[{"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"creator":"dernst","file_id":"12842","relation":"main_file","success":1,"access_level":"open_access","content_type":"application/pdf","file_name":"2023_DevelopmentalCell_Huljev.pdf","date_updated":"2023-04-17T07:41:25Z","file_size":7925886,"checksum":"c80ca2ebc241232aacdb5aa4b4c80957","date_created":"2023-04-17T07:41:25Z"}],"date_published":"2023-04-10T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"language":[{"iso":"eng"}],"publication":"Developmental Cell","has_accepted_license":"1","month":"04","oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"ALTF 850-2017","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation","_id":"26520D1E-B435-11E9-9278-68D0E5697425"},{"grant_number":"LT000429","name":"Coordination of mesendoderm fate specification and internalization during zebrafish gastrulation","_id":"266BC5CE-B435-11E9-9278-68D0E5697425"}],"ddc":["570"],"volume":58,"acknowledgement":"We thank Andrea Pauli (IMP) and Edouard Hannezo (ISTA) for fruitful discussions and support with the SPIM experiments; the Heisenberg group, and especially Feyza Nur Arslan and Alexandra Schauer, for discussions and feedback; Michaela Jović (ISTA) for help with the quantitative real-time PCR protocol; the bioimaging and zebrafish facilities of ISTA for continuous support; Stephan Preibisch (Janelia Research Campus) for support with the SPIM data analysis; and Nobuhiro Nakamura (Tokyo Institute of Technology) for sharing α1-Na+/K+-ATPase antibody. This work was supported by funding from the European Union (European Research Council Advanced grant 742573 to C.-P.H.), postdoctoral fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P., and a PhD fellowship from the Studienstiftung des deutschen Volkes to F.P.","isi":1,"external_id":{"isi":["000982111800001"]},"date_updated":"2023-08-01T14:10:38Z","year":"2023","citation":{"ista":"Huljev K, Shamipour S, Nunes Pinheiro DC, Preusser F, Steccari I, Sommer CM, Naik S, Heisenberg C-PJ. 2023. A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. Developmental Cell. 58(7), 582–596.e7.","mla":"Huljev, Karla, et al. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” <i>Developmental Cell</i>, vol. 58, no. 7, Elsevier, 2023, p. 582–596.e7, doi:<a href=\"https://doi.org/10.1016/j.devcel.2023.02.016\">10.1016/j.devcel.2023.02.016</a>.","short":"K. Huljev, S. Shamipour, D.C. Nunes Pinheiro, F. Preusser, I. Steccari, C.M. Sommer, S. Naik, C.-P.J. Heisenberg, Developmental Cell 58 (2023) 582–596.e7.","ieee":"K. Huljev <i>et al.</i>, “A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish,” <i>Developmental Cell</i>, vol. 58, no. 7. Elsevier, p. 582–596.e7, 2023.","chicago":"Huljev, Karla, Shayan Shamipour, Diana C Nunes Pinheiro, Friedrich Preusser, Irene Steccari, Christoph M Sommer, Suyash Naik, and Carl-Philipp J Heisenberg. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” <i>Developmental Cell</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.devcel.2023.02.016\">https://doi.org/10.1016/j.devcel.2023.02.016</a>.","ama":"Huljev K, Shamipour S, Nunes Pinheiro DC, et al. A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. <i>Developmental Cell</i>. 2023;58(7):582-596.e7. doi:<a href=\"https://doi.org/10.1016/j.devcel.2023.02.016\">10.1016/j.devcel.2023.02.016</a>","apa":"Huljev, K., Shamipour, S., Nunes Pinheiro, D. C., Preusser, F., Steccari, I., Sommer, C. M., … Heisenberg, C.-P. J. (2023). A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2023.02.016\">https://doi.org/10.1016/j.devcel.2023.02.016</a>"},"abstract":[{"lang":"eng","text":"Interstitial fluid (IF) accumulation between embryonic cells is thought to be important for embryo patterning and morphogenesis. Here, we identify a positive mechanical feedback loop between cell migration and IF relocalization and find that it promotes embryonic axis formation during zebrafish gastrulation. We show that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between the yolk cell and deep cell tissue to extend the embryonic axis, compress the overlying deep cell layer, thereby causing IF to flow from the deep cell layer to the boundary between the yolk cell and the deep cell layer, directly ahead of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion formation and migration by opening up the space into which the ppl moves and, thereby, the ability of the ppl to trigger IF relocalization by pushing against the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic feedback loop between cell migration and IF relocalization."}],"doi":"10.1016/j.devcel.2023.02.016","day":"10","file_date_updated":"2023-04-17T07:41:25Z","page":"582-596.e7","quality_controlled":"1","ec_funded":1,"article_type":"original","publisher":"Elsevier","author":[{"full_name":"Huljev, Karla","first_name":"Karla","last_name":"Huljev","id":"44C6F6A6-F248-11E8-B48F-1D18A9856A87"},{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","full_name":"Shamipour, Shayan","first_name":"Shayan","last_name":"Shamipour"},{"full_name":"Nunes Pinheiro, Diana C","orcid":"0000-0003-4333-7503","last_name":"Nunes Pinheiro","first_name":"Diana C","id":"2E839F16-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Friedrich","last_name":"Preusser","full_name":"Preusser, Friedrich"},{"last_name":"Steccari","first_name":"Irene","full_name":"Steccari, Irene","id":"2705C766-9FE2-11EA-B224-C6773DDC885E"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"id":"2C0B105C-F248-11E8-B48F-1D18A9856A87","full_name":"Naik, Suyash","orcid":"0000-0001-8421-5508","last_name":"Naik","first_name":"Suyash"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"issue":"7","_id":"12830","scopus_import":"1","title":"A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish","intvolume":"        58","publication_status":"published","article_processing_charge":"Yes (via OA deal)","date_created":"2023-04-16T22:01:07Z","department":[{"_id":"CaHe"},{"_id":"Bio"}]},{"related_material":{"record":[{"relation":"earlier_version","id":"9750","status":"public"}]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","file":[{"file_id":"10780","creator":"dernst","success":1,"relation":"main_file","access_level":"open_access","date_updated":"2022-02-21T08:45:11Z","file_name":"2022_PNAS_Slovakova.pdf","content_type":"application/pdf","date_created":"2022-02-21T08:45:11Z","checksum":"d49f83c3580613966f71768ddb9a55a5","file_size":1609678}],"oa":1,"publication_identifier":{"eissn":["10916490"]},"date_published":"2022-02-14T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"language":[{"iso":"eng"}],"month":"02","article_number":"e2122030119","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"}],"oa_version":"Published Version","project":[{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"},{"call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573"},{"_id":"2521E28E-B435-11E9-9278-68D0E5697425","name":"Modulation of adhesion function in cell-cell contact formation by cortical tension","grant_number":"187-2013"}],"publication":"Proceedings of the National Academy of Sciences of the United States of America","has_accepted_license":"1","ddc":["570"],"acknowledgement":"We thank Guillaume Salbreaux, Silvia Grigolon, Edouard Hannezo, and Vanessa Barone for discussions and comments on the manuscript and Shayan Shamipour and Daniel Capek for help with data analysis. We also thank the Imaging & Optics, Electron Microscopy, and Zebrafish Facility Scientific Service Units at the Institute of Science and Technology Austria (ISTA)Nasser Darwish-Miranda  for continuous support. We acknowledge Hitoshi Morita for the gift of VinculinB-GFP plasmid. This research was supported by an ISTA Fellow Marie-Curie Co-funding of regional, national, and international programmes Grant P_IST_EU01 (to J.S.), European Molecular Biology Organization Long-Term Fellowship Grant, ALTF reference number: 187-2013 (to M.S.), Schroedinger Fellowship J4332-B28 (to M.S.), and European Research Council Advanced Grant (MECSPEC; to C.-P.H.).","volume":119,"abstract":[{"lang":"eng","text":"Tension of the actomyosin cell cortex plays a key role in determining cell–cell contact growth and size. The level of cortical tension outside of the cell–cell contact, when pulling at the contact edge, scales with the total size to which a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell–cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell–cell contact size is limited by tension-stabilizing E-cadherin–actin complexes at the contact."}],"doi":"10.1073/pnas.2122030119","day":"14","isi":1,"external_id":{"isi":["000766926900009"]},"date_updated":"2023-08-02T14:26:51Z","citation":{"ama":"Slovakova J, Sikora MK, Arslan FN, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2022;119(8). doi:<a href=\"https://doi.org/10.1073/pnas.2122030119\">10.1073/pnas.2122030119</a>","apa":"Slovakova, J., Sikora, M. K., Arslan, F. N., Caballero Mancebo, S., Krens, G., Kaufmann, W., … Heisenberg, C.-P. J. (2022). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. Proceedings of the National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2122030119\">https://doi.org/10.1073/pnas.2122030119</a>","chicago":"Slovakova, Jana, Mateusz K Sikora, Feyza N Arslan, Silvia Caballero Mancebo, Gabriel Krens, Walter Kaufmann, Jack Merrin, and Carl-Philipp J Heisenberg. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. Proceedings of the National Academy of Sciences, 2022. <a href=\"https://doi.org/10.1073/pnas.2122030119\">https://doi.org/10.1073/pnas.2122030119</a>.","ieee":"J. Slovakova <i>et al.</i>, “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 8. Proceedings of the National Academy of Sciences, 2022.","mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 8, e2122030119, Proceedings of the National Academy of Sciences, 2022, doi:<a href=\"https://doi.org/10.1073/pnas.2122030119\">10.1073/pnas.2122030119</a>.","short":"J. Slovakova, M.K. Sikora, F.N. Arslan, S. Caballero Mancebo, G. Krens, W. Kaufmann, J. Merrin, C.-P.J. Heisenberg, Proceedings of the National Academy of Sciences of the United States of America 119 (2022).","ista":"Slovakova J, Sikora MK, Arslan FN, Caballero Mancebo S, Krens G, Kaufmann W, Merrin J, Heisenberg C-PJ. 2022. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. Proceedings of the National Academy of Sciences of the United States of America. 119(8), e2122030119."},"year":"2022","article_type":"original","publisher":"Proceedings of the National Academy of Sciences","file_date_updated":"2022-02-21T08:45:11Z","ec_funded":1,"quality_controlled":"1","title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells","intvolume":"       119","publication_status":"published","article_processing_charge":"No","department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"date_created":"2022-02-20T23:01:31Z","author":[{"full_name":"Slovakova, Jana","first_name":"Jana","last_name":"Slovakova","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Mateusz K","last_name":"Sikora","full_name":"Sikora, Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87"},{"id":"49DA7910-F248-11E8-B48F-1D18A9856A87","first_name":"Feyza N","last_name":"Arslan","orcid":"0000-0001-5809-9566","full_name":"Arslan, Feyza N"},{"orcid":"0000-0002-5223-3346","full_name":"Caballero Mancebo, Silvia","first_name":"Silvia","last_name":"Caballero Mancebo","id":"2F1E1758-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","last_name":"Krens","first_name":"Gabriel","id":"2B819732-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","first_name":"Walter","last_name":"Kaufmann","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"id":"4515C308-F248-11E8-B48F-1D18A9856A87","first_name":"Jack","last_name":"Merrin","orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack"},{"orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"issue":"8","_id":"10766","scopus_import":"1"},{"abstract":[{"text":"The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general.","lang":"eng"}],"doi":"10.1093/oons/kvac009","day":"07","date_updated":"2023-11-30T10:55:12Z","citation":{"ieee":"A. H. Hansen <i>et al.</i>, “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1. Oxford Academic, 2022.","chicago":"Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>. Oxford Academic, 2022. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>.","apa":"Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter, S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. Oxford Academic. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>","ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. 2022;1(1). doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>","ista":"Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM, Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 1(1), kvac009.","short":"A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter, C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford Open Neuroscience 1 (2022).","mla":"Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1, kvac009, Oxford Academic, 2022, doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>."},"year":"2022","ddc":["570"],"acknowledgement":"A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics Facility, Lab Support Facility and Preclinical Facility.","volume":1,"title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","intvolume":"         1","publication_status":"published","article_processing_charge":"No","department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"date_created":"2022-02-25T07:52:11Z","author":[{"full_name":"Hansen, Andi H","first_name":"Andi H","last_name":"Hansen","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Florian","last_name":"Pauler","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"id":"3BE60946-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4844-6311","full_name":"Riedl, Michael","first_name":"Michael","last_name":"Riedl"},{"last_name":"Streicher","first_name":"Carmen","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Heger, Anna-Magdalena","last_name":"Heger","first_name":"Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87"},{"id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","first_name":"Susanne","last_name":"Laukoter"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","last_name":"Nicolas","first_name":"Armel"},{"id":"3A374330-F248-11E8-B48F-1D18A9856A87","full_name":"Hof, Björn","orcid":"0000-0003-2057-2754","last_name":"Hof","first_name":"Björn"},{"first_name":"Li Huei","last_name":"Tsai","full_name":"Tsai, Li Huei"},{"full_name":"Rülicke, Thomas","first_name":"Thomas","last_name":"Rülicke"},{"last_name":"Hippenmeyer","first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"issue":"1","_id":"10791","article_type":"original","publisher":"Oxford Academic","file_date_updated":"2023-08-16T08:00:30Z","ec_funded":1,"quality_controlled":"1","oa":1,"publication_identifier":{"eissn":["2753-149X"]},"date_published":"2022-07-07T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"record":[{"id":"12726","relation":"dissertation_contains","status":"public"},{"id":"14530","relation":"dissertation_contains","status":"public"}]},"status":"public","file":[{"date_created":"2023-08-16T08:00:30Z","checksum":"822e76e056c07099d1fb27d1ece5941b","file_size":4846551,"date_updated":"2023-08-16T08:00:30Z","file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","content_type":"application/pdf","relation":"main_file","success":1,"access_level":"open_access","file_id":"14061","creator":"dernst"}],"month":"07","article_number":"kvac009","oa_version":"Published Version","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"project":[{"grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"publication":"Oxford Open Neuroscience","has_accepted_license":"1","language":[{"iso":"eng"}]},{"publication_identifier":{"issn":["2663-337X"]},"oa":1,"supervisor":[{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","first_name":"Peter M","last_name":"Jonas"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"type":"dissertation","date_published":"2022-04-20T00:00:00Z","file":[{"date_updated":"2023-04-20T22:30:03Z","content_type":"application/pdf","file_name":"Olena_KIM_thesis_final.pdf","embargo":"2023-04-19","date_created":"2022-04-20T14:21:56Z","checksum":"1616a8bf6f13a57c892dac873dcd0936","file_size":21273537,"file_id":"11220","creator":"okim","relation":"main_file","access_level":"open_access"},{"access_level":"closed","relation":"source_file","creator":"okim","file_id":"11221","embargo_to":"open_access","file_size":59248569,"checksum":"1acb433f98dc42abb0b4b0cbb0c4b918","date_created":"2022-04-20T14:22:56Z","file_name":"KIM_thesis_final.zip","content_type":"application/x-zip-compressed","date_updated":"2023-04-20T22:30:03Z"}],"status":"public","related_material":{"record":[{"relation":"part_of_dissertation","id":"11222","status":"public"},{"status":"public","id":"7473","relation":"part_of_dissertation"}]},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","project":[{"grant_number":"708497","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse","call_identifier":"H2020","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","name":"Zellkommunikation in Gesundheit und Krankheit","grant_number":"W01205"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"month":"04","has_accepted_license":"1","language":[{"iso":"eng"}],"day":"20","doi":"10.15479/at:ista:11196","degree_awarded":"PhD","abstract":[{"lang":"eng","text":"One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). \r\n\tIn addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.\r\n"}],"citation":{"ista":"Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria.","short":"O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses, Institute of Science and Technology Austria, 2022.","mla":"Kim, Olena. <i>Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11196\">10.15479/at:ista:11196</a>.","chicago":"Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11196\">https://doi.org/10.15479/at:ista:11196</a>.","ieee":"O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022.","apa":"Kim, O. (2022). <i>Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11196\">https://doi.org/10.15479/at:ista:11196</a>","ama":"Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11196\">10.15479/at:ista:11196</a>"},"year":"2022","date_updated":"2023-08-18T06:31:52Z","ddc":["570"],"date_created":"2022-04-20T09:47:12Z","department":[{"_id":"PeJo"},{"_id":"GradSch"}],"article_processing_charge":"No","publication_status":"published","alternative_title":["ISTA Thesis"],"title":"Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses","_id":"11196","author":[{"first_name":"Olena","last_name":"Kim","full_name":"Kim, Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Institute of Science and Technology Austria","ec_funded":1,"page":"132","file_date_updated":"2023-04-20T22:30:03Z"},{"status":"public","related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/"}]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"date_updated":"2023-03-21T14:18:10Z","content_type":"application/pdf","file_name":"sciadv.abq1263.pdf","date_created":"2023-03-21T14:18:10Z","file_size":2973998,"checksum":"0117023e188542082ca6693cf39e7f03","file_id":"12742","creator":"patrickd","relation":"main_file","success":1,"access_level":"open_access"}],"oa":1,"publication_identifier":{"issn":["2375-2548"]},"date_published":"2022-11-01T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"language":[{"iso":"eng"}],"month":"11","article_number":"abq1263","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"oa_version":"Published Version","project":[{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"},{"call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression"}],"publication":"Science Advances","has_accepted_license":"1","ddc":["570"],"acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS  Unit)  and  S.  Gharagozlou  for  technical  support.  This  research  was  supported  by  the  Scientific  Service  Units  (SSU)  of  IST  Austria  through  resources  provided  by  the  Imaging  &  Optics Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A. received funding   from   the   FWF   Firnberg-Programm   (T   1031).   The   work   was   supported   by   IST   institutional  funds  and  by  the  European  Research  Council  (ERC)  under  the  European  Union’s  Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H.","volume":8,"abstract":[{"lang":"eng","text":"The generation of a correctly-sized cerebral cortex with all-embracing neuronal and glial cell-type diversity critically depends on faithful radial glial progenitor (RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene expression instructs RGP lineage progression is unknown. Here we utilize Mosaic Analysis with Double Markers (MADM)-based single cell technology and demonstrate that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts at the global tissue-wide level. Conversely, cortical astrocyte production and maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation. We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression that are dependent on complex interplays between intrinsic and tissue-wide properties. In a broader context our results imply a critical role for the genetic and cellular niche environment in neural stem cell behavior."}],"doi":"10.1126/sciadv.abq1263","day":"01","date_updated":"2023-05-31T12:24:10Z","citation":{"mla":"Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” <i>Science Advances</i>, vol. 8, no. 44, abq1263, American Association for the Advancement of Science, 2022, doi:<a href=\"https://doi.org/10.1126/sciadv.abq1263\">10.1126/sciadv.abq1263</a>.","short":"N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).","ista":"Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. Science Advances. 8(44), abq1263.","apa":"Amberg, N., Pauler, F., Streicher, C., &#38; Hippenmeyer, S. (2022). Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.abq1263\">https://doi.org/10.1126/sciadv.abq1263</a>","ama":"Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. <i>Science Advances</i>. 2022;8(44). doi:<a href=\"https://doi.org/10.1126/sciadv.abq1263\">10.1126/sciadv.abq1263</a>","chicago":"Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” <i>Science Advances</i>. American Association for the Advancement of Science, 2022. <a href=\"https://doi.org/10.1126/sciadv.abq1263\">https://doi.org/10.1126/sciadv.abq1263</a>.","ieee":"N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression,” <i>Science Advances</i>, vol. 8, no. 44. American Association for the Advancement of Science, 2022."},"year":"2022","article_type":"original","publisher":"American Association for the Advancement of Science","file_date_updated":"2023-03-21T14:18:10Z","ec_funded":1,"quality_controlled":"1","title":"Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression","intvolume":"         8","publication_status":"published","department":[{"_id":"SiHi"}],"date_created":"2022-04-26T15:04:50Z","article_processing_charge":"No","author":[{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","first_name":"Nicole"},{"last_name":"Pauler","first_name":"Florian","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","first_name":"Carmen","full_name":"Streicher, Carmen"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"issue":"44","_id":"11336","scopus_import":"1"},{"year":"2022","citation":{"short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022).","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>, vol. 11, e78995, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>."},"date_updated":"2023-08-03T12:54:21Z","external_id":{"isi":["000838410200001"]},"isi":1,"day":"26","doi":"10.7554/eLife.78995","abstract":[{"text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.","lang":"eng"}],"volume":11,"acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","ddc":["570"],"scopus_import":"1","_id":"11843","author":[{"first_name":"Kathrin","last_name":"Tomasek","full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Glatzová, Ivana","last_name":"Glatzová","first_name":"Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d"},{"first_name":"Michael S.","last_name":"Lukesch","full_name":"Lukesch, Michael S."},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"}],"department":[{"_id":"MiSi"},{"_id":"CaGu"}],"article_processing_charge":"Yes","date_created":"2022-08-14T22:01:46Z","publication_status":"published","intvolume":"        11","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","quality_controlled":"1","ec_funded":1,"file_date_updated":"2022-08-16T08:57:37Z","publisher":"eLife Sciences Publications","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2022-07-26T00:00:00Z","publication_identifier":{"eissn":["2050-084X"]},"oa":1,"file":[{"content_type":"application/pdf","file_name":"2022_eLife_Tomasek.pdf","date_updated":"2022-08-16T08:57:37Z","file_size":2057577,"checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","date_created":"2022-08-16T08:57:37Z","creator":"cchlebak","file_id":"11861","success":1,"access_level":"open_access","relation":"main_file"}],"status":"public","related_material":{"record":[{"id":"10316","relation":"earlier_version","status":"public"}]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","has_accepted_license":"1","publication":"eLife","project":[{"call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular navigation along spatial gradients"},{"grant_number":"P29911","name":"Mechanical adaptation of lamellipodial actin","call_identifier":"FWF","_id":"26018E70-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"article_number":"e78995","month":"07","language":[{"iso":"eng"}]},{"author":[{"id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","last_name":"Schulz","first_name":"Rouven","full_name":"Schulz, Rouven","orcid":"0000-0001-5297-733X"}],"_id":"11945","title":"Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function","alternative_title":["ISTA Thesis"],"date_created":"2022-08-23T11:33:11Z","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"article_processing_charge":"No","publication_status":"published","file_date_updated":"2022-08-25T09:33:31Z","page":"133","publisher":"Institute of Science and Technology Austria","year":"2022","citation":{"mla":"Schulz, Rouven. <i>Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11945\">10.15479/at:ista:11945</a>.","short":"R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function, Institute of Science and Technology Austria, 2022.","ista":"Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria.","ama":"Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11945\">10.15479/at:ista:11945</a>","apa":"Schulz, R. (2022). <i>Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11945\">https://doi.org/10.15479/at:ista:11945</a>","chicago":"Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11945\">https://doi.org/10.15479/at:ista:11945</a>.","ieee":"R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function,” Institute of Science and Technology Austria, 2022."},"date_updated":"2023-08-03T13:02:26Z","abstract":[{"lang":"eng","text":"G protein-coupled receptors (GPCRs) respond to specific ligands and regulate multiple processes ranging from cell growth and immune responses to neuronal signal transmission. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additional challenges exist to dissect cell-type specific responses when the same GPCR is expressed on several cell types within the body. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable responses on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Since β2AR is also enriched in microglia, which can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR in primary microglia and successfully recapitulate β2AR-mediated filopodia formation through CNO stimulation. To dissect the role of selected GPCRs during microglial inflammation, we additionally generated DREADD-based chimeras for microglia-enriched GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65 both modulated the inflammatory response with a similar profile as endogenously expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach provides the means to obtain mechanistic and functional insights into GPCR signaling on a cell-type specific level."}],"day":"23","degree_awarded":"PhD","doi":"10.15479/at:ista:11945","ddc":["570"],"has_accepted_license":"1","month":"08","project":[{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"oa_version":"Published Version","language":[{"iso":"eng"}],"type":"dissertation","date_published":"2022-08-23T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"supervisor":[{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra"}],"publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"status":"public","id":"11995","relation":"dissertation_contains"}]},"status":"public","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","file":[{"success":1,"access_level":"open_access","relation":"main_file","creator":"rschulz","file_id":"11970","file_size":28079331,"checksum":"61b1b666a210ff7cdd0e95ea75207a13","date_created":"2022-08-25T08:59:57Z","content_type":"application/pdf","file_name":"Thesis_Rouven_Schulz_2022_final.pdf","date_updated":"2022-08-25T08:59:57Z"},{"date_created":"2022-08-25T09:00:11Z","checksum":"2b8f95ea1c134dbdb927b41b1dbeeeb5","file_size":27226963,"date_updated":"2022-08-25T09:33:31Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"Thesis_Rouven_Schulz_2022_final.docx","access_level":"closed","relation":"source_file","file_id":"11971","creator":"rschulz"}]},{"language":[{"iso":"eng"}],"month":"08","article_number":"4728","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"oa_version":"Published Version","project":[{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"publication":"Nature Communications","has_accepted_license":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","related_material":{"link":[{"url":"https://ista.ac.at/en/news/dreaddful-mimicry/","relation":"press_release","description":"News on ISTA website"}],"record":[{"status":"public","relation":"part_of_dissertation","id":"11945"},{"id":"11542","relation":"research_data","status":"public"}]},"file":[{"relation":"main_file","success":1,"access_level":"open_access","creator":"cchlebak","file_id":"12002","checksum":"191d9db0266e14a28d3a56dc7f65da84","file_size":7317396,"date_created":"2022-08-29T06:44:30Z","content_type":"application/pdf","file_name":"2022_NatComm_Schulz.pdf","date_updated":"2022-08-29T06:44:30Z"}],"oa":1,"publication_identifier":{"eissn":["2041-1723"]},"date_published":"2022-08-15T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_type":"original","publisher":"Springer Nature","file_date_updated":"2022-08-29T06:44:30Z","quality_controlled":"1","title":"Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses","intvolume":"        13","publication_status":"published","article_processing_charge":"No","date_created":"2022-08-28T22:01:59Z","department":[{"_id":"SaSi"}],"author":[{"full_name":"Schulz, Rouven","orcid":"0000-0001-5297-733X","last_name":"Schulz","first_name":"Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Korkut","first_name":"Medina","full_name":"Korkut, Medina","orcid":"0000-0003-4309-2251","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","last_name":"Colombo","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria"},{"full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"pmid":1,"_id":"11995","scopus_import":"1","ddc":["570"],"volume":13,"acknowledgement":"The authors thank the Scientific Service Units at ISTA, in particular the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility, and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco Benevento for sharing reagents and expertise. This research was supported by a DOC Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences.","abstract":[{"text":"G protein-coupled receptors (GPCRs) regulate processes ranging from immune responses to neuronal signaling. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additionally, dissecting cell type-specific responses is challenging when the same GPCR is expressed on different cells within a tissue. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest. We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation in microglia, an immune cell capable of driving central nervous system inflammation. When dissecting microglial inflammation, we included two additional DREADD-based chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65 modulate the inflammatory response with high similarity to endogenous β2AR, while DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation of cell type-dependent pathways without known endogenous ligands.","lang":"eng"}],"doi":"10.1038/s41467-022-32390-1","day":"15","isi":1,"external_id":{"isi":["000840984400032"],"pmid":["35970889"]},"date_updated":"2024-02-21T12:34:51Z","year":"2022","citation":{"ista":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. Nature Communications. 13, 4728.","mla":"Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” <i>Nature Communications</i>, vol. 13, 4728, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32390-1\">10.1038/s41467-022-32390-1</a>.","short":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications 13 (2022).","ieee":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","chicago":"Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-32390-1\">https://doi.org/10.1038/s41467-022-32390-1</a>.","ama":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-32390-1\">10.1038/s41467-022-32390-1</a>","apa":"Schulz, R., Korkut, M., Venturino, A., Colombo, G., &#38; Siegert, S. (2022). Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-32390-1\">https://doi.org/10.1038/s41467-022-32390-1</a>"}},{"month":"10","project":[{"grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"name":"Microglia action towards neuronal circuit formation and function in health and disease","grant_number":"715571","_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"oa_version":"Published Version","has_accepted_license":"1","publication":"Nature Neuroscience","keyword":["General Neuroscience"],"language":[{"iso":"eng"}],"oa":1,"publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"type":"journal_article","date_published":"2022-10-01T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","related_material":{"link":[{"url":"https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/","description":"News on ISTA website","relation":"press_release"}],"record":[{"id":"12378","relation":"dissertation_contains","status":"public"}]},"file":[{"creator":"dernst","file_id":"12437","access_level":"open_access","success":1,"relation":"main_file","content_type":"application/pdf","file_name":"2022_NatureNeuroscience_Colombo.pdf","date_updated":"2023-01-30T08:06:56Z","file_size":23789835,"checksum":"28431146873096f52e0107b534f178c9","date_created":"2023-01-30T08:06:56Z"}],"intvolume":"        25","title":"A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes","date_created":"2023-01-16T09:53:07Z","department":[{"_id":"SaSi"}],"article_processing_charge":"No","publication_status":"published","issue":"10","author":[{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","last_name":"Colombo","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria"},{"id":"850B2E12-9CD4-11E9-837F-E719E6697425","full_name":"Cubero, Ryan J","orcid":"0000-0003-0002-1867","last_name":"Cubero","first_name":"Ryan J"},{"full_name":"Kanari, Lida","last_name":"Kanari","first_name":"Lida"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro"},{"last_name":"Schulz","first_name":"Rouven","full_name":"Schulz, Rouven","orcid":"0000-0001-5297-733X","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Scolamiero","first_name":"Martina","full_name":"Scolamiero, Martina"},{"full_name":"Agerberg, Jens","last_name":"Agerberg","first_name":"Jens"},{"full_name":"Mathys, Hansruedi","first_name":"Hansruedi","last_name":"Mathys"},{"first_name":"Li-Huei","last_name":"Tsai","full_name":"Tsai, Li-Huei"},{"full_name":"Chachólski, Wojciech","first_name":"Wojciech","last_name":"Chachólski"},{"full_name":"Hess, Kathryn","first_name":"Kathryn","last_name":"Hess"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","first_name":"Sandra","last_name":"Siegert"}],"scopus_import":"1","pmid":1,"_id":"12244","article_type":"original","publisher":"Springer Nature","file_date_updated":"2023-01-30T08:06:56Z","ec_funded":1,"quality_controlled":"1","page":"1379-1393","abstract":[{"text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to characterize these changes usually involve user-selected morphometric features, which preclude the identification of a spectrum of context-dependent morphological phenotypes. Here we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes and overcomes feature-selection biases and biological variability. We extract spatially heterogeneous and sexually dimorphic morphological phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration mouse models, with females showing a faster morphological shift in affected brain regions. Remarkably, microglia morphologies reflect an adaptation upon repeated exposure to ketamine anesthesia and do not recover to control morphologies. Finally, we demonstrate that both long primary processes and short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs opens a new perspective to characterize microglial morphology.","lang":"eng"}],"day":"01","doi":"10.1038/s41593-022-01167-6","external_id":{"pmid":["36180790"],"isi":["000862214700001"]},"isi":1,"citation":{"short":"G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero, J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature Neuroscience 25 (2022) 1379–1393.","mla":"Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>, vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>.","ista":"Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience. 25(10), 1379–1393.","apa":"Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero, M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>","ama":"Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. 2022;25(10):1379-1393. doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>","chicago":"Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>.","ieee":"G. Colombo <i>et al.</i>, “A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes,” <i>Nature Neuroscience</i>, vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022."},"year":"2022","date_updated":"2024-03-25T23:30:10Z","ddc":["570"],"acknowledgement":"We thank the scientific service units at ISTA, in particular M. Schunn’s team at the preclinical facility, and especially our colony manager S. Haslinger, for excellent support. We are also grateful to the ISTA Imaging & Optics Facility, and in particular C. Sommer for helping with the data file conversions. We thank R. Erhart from the ISTA Scientific Computing Unit for improving the script performance. We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert group for constant feedback on the project and on the manuscript. This research was supported by the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","volume":25},{"file":[{"file_name":"2022_eLife_Sumser.pdf","content_type":"application/pdf","date_updated":"2023-01-30T11:50:53Z","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","file_size":8506811,"date_created":"2023-01-30T11:50:53Z","creator":"dernst","file_id":"12463","access_level":"open_access","success":1,"relation":"main_file"}],"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2022-09-15T00:00:00Z","type":"journal_article","publication_identifier":{"eissn":["2050-084X"]},"oa":1,"language":[{"iso":"eng"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"publication":"eLife","has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"oa_version":"Published Version","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"_id":"2634E9D2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Circuits of Visual Attention","grant_number":"756502"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"_id":"266D407A-B435-11E9-9278-68D0E5697425","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","grant_number":"LT000256"},{"_id":"264FEA02-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1098-2017","name":"Connecting sensory with motor processing in the superior colliculus"}],"month":"09","article_number":"79848","volume":11,"acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).","ddc":["570"],"date_updated":"2023-08-04T10:29:48Z","citation":{"chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>.","ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022)."},"year":"2022","isi":1,"external_id":{"pmid":["36040301"],"isi":["000892204300001"]},"doi":"10.7554/elife.79848","day":"15","abstract":[{"text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo.","lang":"eng"}],"quality_controlled":"1","ec_funded":1,"file_date_updated":"2023-01-30T11:50:53Z","publisher":"eLife Sciences Publications","article_type":"original","pmid":1,"_id":"12288","scopus_import":"1","author":[{"id":"3320A096-F248-11E8-B48F-1D18A9856A87","first_name":"Anton L","last_name":"Sumser","orcid":"0000-0002-4792-1881","full_name":"Sumser, Anton L"},{"first_name":"Maximilian A","last_name":"Jösch","orcid":"0000-0002-3937-1330","full_name":"Jösch, Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"},{"full_name":"Ben Simon, Yoav","first_name":"Yoav","last_name":"Ben Simon","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"}],"publication_status":"published","date_created":"2023-01-16T10:04:15Z","article_processing_charge":"No","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","intvolume":"        11"},{"language":[{"iso":"eng"}],"month":"11","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"oa_version":"Published Version","project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program"}],"has_accepted_license":"1","status":"public","related_material":{"record":[{"status":"public","id":"12244","relation":"part_of_dissertation"}]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"access_level":"closed","relation":"source_file","creator":"cchlebak","file_id":"12379","file_size":23890382,"checksum":"8cd3ddfe9b53381dcf086023d8d8893a","embargo_to":"open_access","date_created":"2023-01-25T14:31:32Z","file_name":"Gloria_Colombo_Thesis.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2023-04-12T22:30:03Z"},{"access_level":"open_access","relation":"main_file","creator":"cchlebak","file_id":"12380","file_size":13802421,"checksum":"8af4319c18b516e8758e9a6cb02b103b","embargo":"2023-04-11","date_created":"2023-01-25T14:31:36Z","file_name":"Gloria_Colombo_Thesis.pdf","content_type":"application/pdf","date_updated":"2023-04-12T22:30:03Z"}],"supervisor":[{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877"}],"oa":1,"publication_identifier":{"issn":["2663-337X"]},"date_published":"2022-11-11T00:00:00Z","type":"dissertation","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publisher":"Institute of Science and Technology Austria","file_date_updated":"2023-04-12T22:30:03Z","page":"142","ec_funded":1,"title":"MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes","alternative_title":["ISTA Thesis"],"publication_status":"published","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"article_processing_charge":"No","date_created":"2023-01-25T14:27:43Z","author":[{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","first_name":"Gloria","last_name":"Colombo"}],"_id":"12378","ddc":["570"],"abstract":[{"lang":"eng","text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to \r\ncharacterize these changes usually involve user-selected morphometric features, which \r\npreclude the identification of a spectrum of context-dependent morphological phenotypes. \r\nHere, we develop MorphOMICs, a topological data analysis approach, which enables semi\u0002automatic mapping of microglial morphology into an atlas of cue-dependent phenotypes,\r\novercomes feature-selection bias and minimizes biological variability. \r\nFirst, with MorphOMICs we derive the morphological spectrum of microglia across seven \r\nbrain regions during postnatal development and in two distinct Alzheimer’s disease \r\ndegeneration mouse models. We uncover region-specific and sexually dimorphic\r\nmorphological trajectories, with females showing an earlier morphological shift than males in \r\nthe degenerating brain. Overall, we demonstrate that both long primary- and short terminal \r\nprocesses provide distinct insights to morphological phenotypes. Moreover, using machine \r\nlearning to map novel condition on the spectrum, we observe that microglia morphologies \r\nreflect a dose-dependent adaptation upon ketamine anesthesia and do not recover to control \r\nmorphologies.\r\nNext, we took advantage of MorphOMICs to build a high-resolution and layer-specific map of \r\nmicroglial morphological spectrum in the retina, covering postnatal development and rd10 \r\ndegeneration. Here, following photoreceptor death, microglia assume an early development\u0002like morphology. Finally, we map microglial morphology following optic nerve crush on the \r\nretinal spectrum and observe a layer- and sex-dependent response. \r\nOverall, MorphOMICs opens a new perspective to analyze microglial morphology across \r\nmultiple conditions, and provides a novel tool to characterize microglial morphology beyond \r\nthe traditionally dichotomized view of microglia."}],"degree_awarded":"PhD","doi":"10.15479/at:ista:12378","day":"11","date_updated":"2023-08-04T09:40:37Z","citation":{"ieee":"G. Colombo, “MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes,” Institute of Science and Technology Austria, 2022.","chicago":"Colombo, Gloria. “MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12378\">https://doi.org/10.15479/at:ista:12378</a>.","apa":"Colombo, G. (2022). <i>MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12378\">https://doi.org/10.15479/at:ista:12378</a>","ama":"Colombo G. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12378\">10.15479/at:ista:12378</a>","ista":"Colombo G. 2022. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. Institute of Science and Technology Austria.","mla":"Colombo, Gloria. <i>MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12378\">10.15479/at:ista:12378</a>.","short":"G. Colombo, MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes, Institute of Science and Technology Austria, 2022."},"year":"2022"},{"file_date_updated":"2022-07-25T07:11:32Z","quality_controlled":"1","ec_funded":1,"page":"1246-1255","article_type":"original","publisher":"Springer Nature","author":[{"first_name":"Frank P","last_name":"Assen","orcid":"0000-0003-3470-6119","full_name":"Assen, Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Abe, Jun","last_name":"Abe","first_name":"Jun"},{"full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","last_name":"Hons","first_name":"Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Shayan","last_name":"Shamipour","full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","last_name":"Kaufmann","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter"},{"id":"D93824F4-D9BA-11E9-BB12-F207E6697425","full_name":"Costanzo, Tommaso","orcid":"0000-0001-9732-3815","last_name":"Costanzo","first_name":"Tommaso"},{"last_name":"Krens","first_name":"Gabriel","full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87"},{"id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus","last_name":"Brown","full_name":"Brown, Markus"},{"full_name":"Ludewig, Burkhard","last_name":"Ludewig","first_name":"Burkhard"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon","last_name":"Hippenmeyer"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Weninger","first_name":"Wolfgang","full_name":"Weninger, Wolfgang"},{"full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","last_name":"Hannezo","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Sanjiv A.","last_name":"Luther","full_name":"Luther, Sanjiv A."},{"first_name":"Jens V.","last_name":"Stein","full_name":"Stein, Jens V."},{"orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","_id":"9794","intvolume":"        23","title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","date_created":"2021-08-06T09:09:11Z","department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"article_processing_charge":"No","publication_status":"published","ddc":["570"],"volume":23,"acknowledgement":"This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.","external_id":{"isi":["000822975900002"]},"isi":1,"citation":{"ista":"Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255.","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>.","short":"F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255.","chicago":"Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>.","ieee":"F. P. Assen <i>et al.</i>, “Multitier mechanics control stromal adaptations in swelling lymph nodes,” <i>Nature Immunology</i>, vol. 23. Springer Nature, pp. 1246–1255, 2022.","ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. 2022;23:1246-1255. doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>","apa":"Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>"},"year":"2022","date_updated":"2023-08-02T06:53:07Z","abstract":[{"lang":"eng","text":"Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion."}],"day":"11","doi":"10.1038/s41590-022-01257-4","language":[{"iso":"eng"}],"has_accepted_license":"1","publication":"Nature Immunology","month":"07","project":[{"grant_number":"724373","name":"Cellular navigation along spatial gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","file":[{"file_size":11475325,"checksum":"628e7b49809f22c75b428842efe70c68","date_created":"2022-07-25T07:11:32Z","content_type":"application/pdf","file_name":"2022_NatureImmunology_Assen.pdf","date_updated":"2022-07-25T07:11:32Z","success":1,"access_level":"open_access","relation":"main_file","creator":"dernst","file_id":"11642"}],"type":"journal_article","date_published":"2022-07-11T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"publication_identifier":{"issn":["1529-2908"],"eissn":["1529-2916"]}},{"acknowledgement":"We thank Prof. Masazumi Tada and Roland Dosch for providing transgenic zebrafish lines, the Heisenberg lab for technical assistance and feedback on the manuscript, and the Bioimaging and Fish facilities of IST Austria for continuous support. This work was funded by an ERC advanced grant (MECSPEC to C.-P.H.).","volume":2218,"date_updated":"2022-06-03T10:57:55Z","citation":{"ista":"Xia P, Heisenberg C-PJ. 2021.Quantifying tissue tension in the granulosa layer after laser surgery. In: Germline Development in the Zebrafish. Methods in Molecular Biology, vol. 2218, 117–128.","short":"P. Xia, C.-P.J. Heisenberg, in:, R. Dosch (Ed.), Germline Development in the Zebrafish, Humana, 2021, pp. 117–128.","mla":"Xia, Peng, and Carl-Philipp J. Heisenberg. “Quantifying Tissue Tension in the Granulosa Layer after Laser Surgery.” <i>Germline Development in the Zebrafish</i>, edited by Roland Dosch, vol. 2218, Humana, 2021, pp. 117–28, doi:<a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">10.1007/978-1-0716-0970-5_10</a>.","chicago":"Xia, Peng, and Carl-Philipp J Heisenberg. “Quantifying Tissue Tension in the Granulosa Layer after Laser Surgery.” In <i>Germline Development in the Zebrafish</i>, edited by Roland Dosch, 2218:117–28. Humana, 2021. <a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">https://doi.org/10.1007/978-1-0716-0970-5_10</a>.","ieee":"P. Xia and C.-P. J. Heisenberg, “Quantifying tissue tension in the granulosa layer after laser surgery,” in <i>Germline Development in the Zebrafish</i>, vol. 2218, R. Dosch, Ed. Humana, 2021, pp. 117–128.","ama":"Xia P, Heisenberg C-PJ. Quantifying tissue tension in the granulosa layer after laser surgery. In: Dosch R, ed. <i>Germline Development in the Zebrafish</i>. Vol 2218. Humana; 2021:117-128. doi:<a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">10.1007/978-1-0716-0970-5_10</a>","apa":"Xia, P., &#38; Heisenberg, C.-P. J. (2021). Quantifying tissue tension in the granulosa layer after laser surgery. In R. Dosch (Ed.), <i>Germline Development in the Zebrafish</i> (Vol. 2218, pp. 117–128). Humana. <a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">https://doi.org/10.1007/978-1-0716-0970-5_10</a>"},"year":"2021","external_id":{"pmid":["33606227"]},"doi":"10.1007/978-1-0716-0970-5_10","day":"20","abstract":[{"text":"Tissue morphogenesis is driven by mechanical forces triggering cell movements and shape changes. Quantitatively measuring tension within tissues is of great importance for understanding the role of mechanical signals acting on the cell and tissue level during morphogenesis. Here we introduce laser ablation as a useful tool to probe tissue tension within the granulosa layer, an epithelial monolayer of somatic cells that surround the zebrafish female gamete during folliculogenesis. We describe in detail how to isolate follicles, mount samples, perform laser surgery, and analyze the data.","lang":"eng"}],"page":"117-128","quality_controlled":"1","ec_funded":1,"publisher":"Humana","editor":[{"last_name":"Dosch","first_name":"Roland","full_name":"Dosch, Roland"}],"pmid":1,"_id":"9245","scopus_import":"1","author":[{"id":"4AB6C7D0-F248-11E8-B48F-1D18A9856A87","first_name":"Peng","last_name":"Xia","orcid":"0000-0002-5419-7756","full_name":"Xia, Peng"},{"first_name":"Carl-Philipp J","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"publication_status":"published","department":[{"_id":"CaHe"}],"date_created":"2021-03-14T23:01:34Z","article_processing_charge":"No","alternative_title":["Methods in Molecular Biology"],"title":"Quantifying tissue tension in the granulosa layer after laser surgery","intvolume":"      2218","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2021-02-20T00:00:00Z","type":"book_chapter","publication_identifier":{"isbn":["978-1-0716-0969-9"],"eissn":["1940-6029"],"issn":["1064-3745"],"eisbn":["978-1-0716-0970-5"]},"language":[{"iso":"eng"}],"keyword":["Tissue tension","Morphogenesis","Laser ablation","Zebrafish folliculogenesis","Granulosa cells"],"publication":"Germline Development in the Zebrafish","oa_version":"None","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"project":[{"grant_number":"742573","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"month":"02"},{"scopus_import":"1","_id":"9316","pmid":1,"issue":"7","author":[{"id":"2A003F6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8451-1195","full_name":"Petridou, Nicoletta","first_name":"Nicoletta","last_name":"Petridou"},{"full_name":"Corominas-Murtra, Bernat","orcid":"0000-0001-9806-5643","last_name":"Corominas-Murtra","first_name":"Bernat","id":"43BE2298-F248-11E8-B48F-1D18A9856A87"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","last_name":"Heisenberg"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","last_name":"Hannezo","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B"}],"department":[{"_id":"CaHe"},{"_id":"EdHa"}],"date_created":"2021-04-11T22:01:14Z","article_processing_charge":"No","publication_status":"published","intvolume":"       184","title":"Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions","quality_controlled":"1","ec_funded":1,"page":"1914-1928.e19","file_date_updated":"2021-06-08T10:04:10Z","publisher":"Elsevier","article_type":"original","citation":{"ista":"Petridou N, Corominas-Murtra B, Heisenberg C-PJ, Hannezo EB. 2021. Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions. Cell. 184(7), 1914–1928.e19.","mla":"Petridou, Nicoletta, et al. “Rigidity Percolation Uncovers a Structural Basis for Embryonic Tissue Phase Transitions.” <i>Cell</i>, vol. 184, no. 7, Elsevier, 2021, p. 1914–1928.e19, doi:<a href=\"https://doi.org/10.1016/j.cell.2021.02.017\">10.1016/j.cell.2021.02.017</a>.","short":"N. Petridou, B. Corominas-Murtra, C.-P.J. Heisenberg, E.B. Hannezo, Cell 184 (2021) 1914–1928.e19.","ieee":"N. Petridou, B. Corominas-Murtra, C.-P. J. Heisenberg, and E. B. Hannezo, “Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions,” <i>Cell</i>, vol. 184, no. 7. Elsevier, p. 1914–1928.e19, 2021.","chicago":"Petridou, Nicoletta, Bernat Corominas-Murtra, Carl-Philipp J Heisenberg, and Edouard B Hannezo. “Rigidity Percolation Uncovers a Structural Basis for Embryonic Tissue Phase Transitions.” <i>Cell</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.cell.2021.02.017\">https://doi.org/10.1016/j.cell.2021.02.017</a>.","ama":"Petridou N, Corominas-Murtra B, Heisenberg C-PJ, Hannezo EB. Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions. <i>Cell</i>. 2021;184(7):1914-1928.e19. doi:<a href=\"https://doi.org/10.1016/j.cell.2021.02.017\">10.1016/j.cell.2021.02.017</a>","apa":"Petridou, N., Corominas-Murtra, B., Heisenberg, C.-P. J., &#38; Hannezo, E. B. (2021). Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2021.02.017\">https://doi.org/10.1016/j.cell.2021.02.017</a>"},"year":"2021","date_updated":"2023-08-07T14:33:59Z","external_id":{"pmid":["33730596"],"isi":["000636734000022"]},"isi":1,"day":"01","doi":"10.1016/j.cell.2021.02.017","abstract":[{"lang":"eng","text":"Embryo morphogenesis is impacted by dynamic changes in tissue material properties, which have been proposed to occur via processes akin to phase transitions (PTs). Here, we show that rigidity percolation provides a simple and robust theoretical framework to predict material/structural PTs of embryonic tissues from local cell connectivity. By using percolation theory, combined with directly monitoring dynamic changes in tissue rheology and cell contact mechanics, we demonstrate that the zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively predict and experimentally verify hallmarks of PTs, including power-law exponents and associated discontinuities of macroscopic observables. Finally, we show that this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions causing random and, consequently, uniform changes in cell connectivity. Collectively, our theoretical and experimental findings reveal the structural basis of material PTs in an organismal context."}],"acknowledgement":"We thank Carl Goodrich and the members of the Heisenberg and Hannezo groups, in particular Reka Korei, for help, technical advice, and discussions; and the Bioimaging and zebrafish facilities of the IST Austria for continuous support. This work was supported by the Elise Richter Program of Austrian Science Fund (FWF) to N.I.P. ( V 736-B26 ) and the European Union (European Research Council Advanced Grant 742573 to C.-P.H. and European Research Council Starting Grant 851288 to E.H.).","volume":184,"ddc":["570"],"has_accepted_license":"1","publication":"Cell","project":[{"grant_number":"742573","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"},{"grant_number":"V00736","name":"Tissue material properties in embryonic development","_id":"2693FD8C-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"oa_version":"Published Version","month":"04","language":[{"iso":"eng"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2021-04-01T00:00:00Z","publication_identifier":{"eissn":["10974172"],"issn":["00928674"]},"oa":1,"file":[{"creator":"cziletti","file_id":"9534","success":1,"relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2021_Cell_Petridou.pdf","date_updated":"2021-06-08T10:04:10Z","checksum":"1e5295fbd9c2a459173ec45a0e8a7c2e","file_size":11405875,"date_created":"2021-06-08T10:04:10Z"}],"related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/embryonic-tissue-undergoes-phase-transition/"}]},"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"author":[{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","last_name":"Morandell","full_name":"Morandell, Jasmin"},{"id":"29A8453C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Lena A","first_name":"Lena A","last_name":"Schwarz"},{"orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","first_name":"Bernadette","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","first_name":"Saren","last_name":"Tasciyan","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Georgi A","last_name":"Dimchev","orcid":"0000-0001-8370-6161","full_name":"Dimchev, Georgi A","id":"38C393BE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Nicolas","first_name":"Armel","full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","first_name":"Caroline","last_name":"Kreuzinger"},{"orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","first_name":"Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Knaus","first_name":"Lisa","full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe","last_name":"Dobler","first_name":"Zoe"},{"last_name":"Cacci","first_name":"Emanuele","full_name":"Cacci, Emanuele"},{"id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur","first_name":"Florian KM"},{"last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"issue":"1","_id":"9429","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","intvolume":"        12","publication_status":"published","date_created":"2021-05-28T11:49:46Z","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"article_processing_charge":"No","file_date_updated":"2021-05-28T12:39:43Z","quality_controlled":"1","ec_funded":1,"article_type":"original","publisher":"Springer Nature","isi":1,"external_id":{"isi":["000658769900010"]},"date_updated":"2024-09-10T12:04:26Z","citation":{"short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>.","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021."},"year":"2021","abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs."}],"doi":"10.1038/s41467-021-23123-x","day":"24","ddc":["572"],"acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","volume":12,"publication":"Nature Communications","has_accepted_license":"1","month":"05","article_number":"3058","acknowledged_ssus":[{"_id":"PreCl"}],"oa_version":"Published Version","project":[{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F07807","name":"Neural stem cells in autism and epilepsy"},{"call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"}],"language":[{"iso":"eng"}],"keyword":["General Biochemistry","Genetics and Molecular Biology"],"date_published":"2021-05-24T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"publication_identifier":{"eissn":["2041-1723"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","related_material":{"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}],"record":[{"relation":"earlier_version","id":"7800","status":"public"},{"relation":"dissertation_contains","id":"12401","status":"public"}]},"status":"public","file":[{"date_updated":"2021-05-28T12:39:43Z","file_name":"2021_NatureCommunications_Morandell.pdf","content_type":"application/pdf","date_created":"2021-05-28T12:39:43Z","checksum":"337e0f7959c35ec959984cacdcb472ba","file_size":9358599,"file_id":"9430","creator":"kschuh","success":1,"relation":"main_file","access_level":"open_access"}]},{"year":"2021","citation":{"chicago":"Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>. Cell Press, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>.","ieee":"X. Contreras <i>et al.</i>, “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” <i>Cell Reports</i>, vol. 35, no. 12. Cell Press, 2021.","ama":"Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. 2021;35(12). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>","apa":"Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>","ista":"Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 35(12), 109274.","short":"X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen, T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo, T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).","mla":"Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>, vol. 35, no. 12, 109274, Cell Press, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>."},"date_updated":"2023-08-10T13:55:00Z","external_id":{"isi":["000664463600016"]},"isi":1,"day":"22","doi":"10.1016/j.celrep.2021.109274","abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division."}],"acknowledgement":"We thank the Bioimaging, Life Science, and Pre-Clinical Facilities at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain, M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance; R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of the Hippenmeyer lab for discussion. This work was supported by National Institutes of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This work also received support from IST Austria institutional funds , FWF SFB F78 to S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.","volume":35,"ddc":["570"],"scopus_import":"1","_id":"9603","issue":"12","author":[{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","last_name":"Contreras","first_name":"Ximena"},{"orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","first_name":"Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Davaatseren, Amarbayasgalan","first_name":"Amarbayasgalan","last_name":"Davaatseren","id":"70ADC922-B424-11E9-99E3-BA18E6697425"},{"full_name":"Hansen, Andi H","last_name":"Hansen","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Johanna","last_name":"Sonntag","full_name":"Sonntag, Johanna","id":"32FE7D7C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Lill","last_name":"Andersen","full_name":"Andersen, Lill"},{"last_name":"Bernthaler","first_name":"Tina","full_name":"Bernthaler, Tina"},{"first_name":"Carmen","last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","full_name":"Heger, Anna-Magdalena","last_name":"Heger","first_name":"Anna-Magdalena"},{"first_name":"Randy L.","last_name":"Johnson","full_name":"Johnson, Randy L."},{"first_name":"Lindsay A.","last_name":"Schwarz","full_name":"Schwarz, Lindsay A."},{"full_name":"Luo, Liqun","first_name":"Liqun","last_name":"Luo"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"}],"article_processing_charge":"No","date_created":"2021-06-27T22:01:48Z","department":[{"_id":"SiHi"},{"_id":"LoSw"},{"_id":"PreCl"}],"publication_status":"published","intvolume":"        35","title":"A genome-wide library of MADM mice for single-cell genetic mosaic analysis","quality_controlled":"1","ec_funded":1,"file_date_updated":"2021-06-28T14:06:24Z","publisher":"Cell Press","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","date_published":"2021-06-22T00:00:00Z","publication_identifier":{"eissn":["22111247"]},"oa":1,"file":[{"creator":"asandaue","file_id":"9613","access_level":"open_access","success":1,"relation":"main_file","content_type":"application/pdf","file_name":"2021_CellReports_Contreras.pdf","date_updated":"2021-06-28T14:06:24Z","checksum":"d49520fdcbbb5c2f883bddb67cee5d77","file_size":7653149,"date_created":"2021-06-28T14:06:24Z"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","related_material":{"link":[{"url":"https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/","description":"News on IST Homepage","relation":"press_release"}]},"has_accepted_license":"1","publication":"Cell Reports","project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812"},{"grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"oa_version":"Published Version","article_number":"109274","month":"06","language":[{"iso":"eng"}]},{"related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/the-twinkle-and-the-brain/"}]},"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"content_type":"application/pdf","file_name":"2021_CellReports_Venturino.pdf","date_updated":"2021-07-19T13:32:17Z","file_size":56388540,"checksum":"f056255f6d01fd9a86b5387635928173","date_created":"2021-07-19T13:32:17Z","creator":"cziletti","file_id":"9693","relation":"main_file","success":1,"access_level":"open_access"}],"date_published":"2021-07-06T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"publication_identifier":{"eissn":["22111247"]},"language":[{"iso":"eng"}],"publication":"Cell Reports","has_accepted_license":"1","month":"07","article_number":"109313","oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"project":[{"name":"International IST Doctoral Program","grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"grant_number":"715571","name":"Microglia action towards neuronal circuit formation and function in health and disease","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425"}],"ddc":["570"],"acknowledgement":"We thank the scientific service units at IST Austria, especially the IST bioimaging facility, the preclinical facility, and, specifically, Michael Schunn and Sonja Haslinger for excellent support; Plexxikon for the PLX food; the Csicsvari group for advice and equipment for in vivo recording; Jürgen Siegert for the light-entrainment design; Marco Benevento, Soledad Gonzalo Cogno, Pat King, and all Siegert group members for constant feedback on the project and manuscript; Lorena Pantano (PILM Bioinformatics Core) for assisting with sample-size determination for OD plasticity experiments; and Ana Morello from MIT for technical assistance with VEPs recordings. This research was supported by a DOC Fellowship from the Austrian Academy of Sciences at the Institute of Science and Technology Austria to R.S., from the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (grants 665385 to G.C.; 754411 to R.J.A.C.), the European Research Council (grant 715571 to S.S.), and the National Eye Institute of the National Institutes of Health under award numbers R01EY029245 (to M.F.B.) and R01EY023037 (diversity supplement to H.D.J-C.).","volume":36,"isi":1,"external_id":{"pmid":["34233180"],"isi":["000670188500004"]},"date_updated":"2023-08-10T14:09:39Z","citation":{"apa":"Venturino, A., Schulz, R., De Jesús-Cortés, H., Maes, M. E., Nagy, B., Reilly-Andújar, F., … Siegert, S. (2021). Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">https://doi.org/10.1016/j.celrep.2021.109313</a>","ama":"Venturino A, Schulz R, De Jesús-Cortés H, et al. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. 2021;36(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">10.1016/j.celrep.2021.109313</a>","ieee":"A. Venturino <i>et al.</i>, “Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,” <i>Cell Reports</i>, vol. 36, no. 1. Elsevier, 2021.","chicago":"Venturino, Alessandro, Rouven Schulz, Héctor De Jesús-Cortés, Margaret E Maes, Balint Nagy, Francis Reilly-Andújar, Gloria Colombo, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">https://doi.org/10.1016/j.celrep.2021.109313</a>.","mla":"Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>, vol. 36, no. 1, 109313, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">10.1016/j.celrep.2021.109313</a>.","short":"A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar, G. Colombo, R.J. Cubero, F.E. Schoot Uiterkamp, M.F. Bear, S. Siegert, Cell Reports 36 (2021).","ista":"Venturino A, Schulz R, De Jesús-Cortés H, Maes ME, Nagy B, Reilly-Andújar F, Colombo G, Cubero RJ, Schoot Uiterkamp FE, Bear MF, Siegert S. 2021. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. Cell Reports. 36(1), 109313."},"year":"2021","abstract":[{"lang":"eng","text":"Perineuronal nets (PNNs), components of the extracellular matrix, preferentially coat parvalbumin-positive interneurons and constrain critical-period plasticity in the adult cerebral cortex. Current strategies to remove PNN are long-lasting, invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic ketamine as a method with minimal behavioral effect. We find that this paradigm strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like plasticity. Microglia are critically involved in PNN loss because they engage with parvalbumin-positive neurons in their defined cortical layer. We identify external 60-Hz light-flickering entrainment to recapitulate microglia-mediated PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques, does not induce PNN loss, suggesting microglia might functionally tune to distinct brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative form of PNN intervention in the healthy adult brain."}],"doi":"10.1016/j.celrep.2021.109313","day":"06","file_date_updated":"2021-07-19T13:32:17Z","quality_controlled":"1","ec_funded":1,"article_type":"original","publisher":"Elsevier","author":[{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino","first_name":"Alessandro"},{"orcid":"0000-0001-5297-733X","full_name":"Schulz, Rouven","first_name":"Rouven","last_name":"Schulz","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87"},{"full_name":"De Jesús-Cortés, Héctor","first_name":"Héctor","last_name":"De Jesús-Cortés"},{"full_name":"Maes, Margaret E","orcid":"0000-0001-9642-1085","last_name":"Maes","first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87"},{"id":"93C65ECC-A6F2-11E9-8DF9-9712E6697425","full_name":"Nagy, Balint","first_name":"Balint","last_name":"Nagy"},{"full_name":"Reilly-Andújar, Francis","first_name":"Francis","last_name":"Reilly-Andújar"},{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","full_name":"Colombo, Gloria","orcid":"0000-0001-9434-8902","last_name":"Colombo","first_name":"Gloria"},{"id":"850B2E12-9CD4-11E9-837F-E719E6697425","full_name":"Cubero, Ryan J","orcid":"0000-0003-0002-1867","last_name":"Cubero","first_name":"Ryan J"},{"last_name":"Schoot Uiterkamp","first_name":"Florianne E","full_name":"Schoot Uiterkamp, Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bear","first_name":"Mark F.","full_name":"Bear, Mark F."},{"first_name":"Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"issue":"1","_id":"9642","pmid":1,"scopus_import":"1","title":"Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain","intvolume":"        36","publication_status":"published","article_processing_charge":"No","department":[{"_id":"SaSi"}],"date_created":"2021-07-11T22:01:16Z"},{"language":[{"iso":"eng"}],"project":[{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"ScienComp"}],"oa_version":"None","month":"10","publication":"Nature","status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","related_material":{"link":[{"url":"https://ist.ac.at/en/news/boosting-the-cells-power-house/","relation":"press_release","description":"News on IST Webpage"}]},"publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"type":"journal_article","date_published":"2021-10-14T00:00:00Z","publisher":"Springer Nature","article_type":"original","quality_controlled":"1","ec_funded":1,"page":"364-367","date_created":"2021-10-17T22:01:17Z","department":[{"_id":"LeSa"}],"article_processing_charge":"No","publication_status":"published","intvolume":"       598","title":"Structure and assembly of the mammalian mitochondrial supercomplex CIII<sub>2</sub>CIV","scopus_import":"1","pmid":1,"_id":"10146","issue":"7880","author":[{"id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87","full_name":"Vercellino, Irene","orcid":"0000-0001-5618-3449","last_name":"Vercellino","first_name":"Irene"},{"last_name":"Sazanov","first_name":"Leonid A","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"acknowledgement":"We thank the pre-clinical facility of the IST Austria and A. Venturino for assistance with the animals; and V.-V. Hodirnau for assistance during the Titan Krios data collection, performed at the IST Austria. The data processing was performed at the IST high-performance computing cluster. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754411.","volume":598,"day":"14","doi":"10.1038/s41586-021-03927-z","abstract":[{"lang":"eng","text":"The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2 (refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in mammals, but in contrast to CICIII2 and the respirasome, to date the only known eukaryotic structures of CIII2CIV1-2 come from Saccharomyces cerevisiae11,12 and plants13, which have different organization. Here we present the first, to our knowledge, structures of mammalian (mouse and ovine) CIII2CIV and its assembly intermediates, in different conformations. We describe the assembly of CIII2CIV from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref. 14) deep into CIII2, while its C terminus is integrated into CIV. Our structures (which include CICIII2 and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2 is asymmetric due to the presence of only one copy of subunit 9, which straddles both monomers and prevents the attachment of a second copy of SCAF1 to CIII2, explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer in the electron transport chain."}],"year":"2021","citation":{"chicago":"Vercellino, Irene, and Leonid A Sazanov. “Structure and Assembly of the Mammalian Mitochondrial Supercomplex CIII<sub>2</sub>CIV.” <i>Nature</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41586-021-03927-z\">https://doi.org/10.1038/s41586-021-03927-z</a>.","ieee":"I. Vercellino and L. A. Sazanov, “Structure and assembly of the mammalian mitochondrial supercomplex CIII<sub>2</sub>CIV,” <i>Nature</i>, vol. 598, no. 7880. Springer Nature, pp. 364–367, 2021.","ama":"Vercellino I, Sazanov LA. Structure and assembly of the mammalian mitochondrial supercomplex CIII<sub>2</sub>CIV. <i>Nature</i>. 2021;598(7880):364-367. doi:<a href=\"https://doi.org/10.1038/s41586-021-03927-z\">10.1038/s41586-021-03927-z</a>","apa":"Vercellino, I., &#38; Sazanov, L. A. (2021). Structure and assembly of the mammalian mitochondrial supercomplex CIII<sub>2</sub>CIV. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-021-03927-z\">https://doi.org/10.1038/s41586-021-03927-z</a>","ista":"Vercellino I, Sazanov LA. 2021. Structure and assembly of the mammalian mitochondrial supercomplex CIII<sub>2</sub>CIV. Nature. 598(7880), 364–367.","short":"I. Vercellino, L.A. Sazanov, Nature 598 (2021) 364–367.","mla":"Vercellino, Irene, and Leonid A. Sazanov. “Structure and Assembly of the Mammalian Mitochondrial Supercomplex CIII<sub>2</sub>CIV.” <i>Nature</i>, vol. 598, no. 7880, Springer Nature, 2021, pp. 364–67, doi:<a href=\"https://doi.org/10.1038/s41586-021-03927-z\">10.1038/s41586-021-03927-z</a>."},"date_updated":"2023-08-14T08:01:21Z","external_id":{"isi":["000704581600001"],"pmid":["34616041"]},"isi":1},{"language":[{"iso":"eng"}],"has_accepted_license":"1","month":"11","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"oa_version":"Published Version","status":"public","related_material":{"record":[{"id":"10316","relation":"part_of_dissertation","status":"public"}]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","file":[{"creator":"ktomasek","file_id":"10308","relation":"main_file","access_level":"open_access","file_name":"ThesisTomasekKathrin.pdf","content_type":"application/pdf","date_updated":"2022-12-20T23:30:05Z","file_size":13266088,"checksum":"b39c9e0ef18d0484d537a67551effd02","embargo":"2022-11-18","date_created":"2021-11-18T15:07:31Z"},{"access_level":"closed","relation":"source_file","creator":"ktomasek","file_id":"10309","embargo_to":"open_access","file_size":7539509,"checksum":"c0c440ee9e5ef1102a518a4f9f023e7c","date_created":"2021-11-18T15:07:46Z","file_name":"ThesisTomasekKathrin.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2022-12-20T23:30:05Z"}],"date_published":"2021-11-18T00:00:00Z","type":"dissertation","supervisor":[{"first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052"}],"oa":1,"publication_identifier":{"issn":["2663-337X"]},"file_date_updated":"2022-12-20T23:30:05Z","page":"73","publisher":"Institute of Science and Technology Austria","author":[{"orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin","first_name":"Kathrin","last_name":"Tomasek","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"}],"_id":"10307","alternative_title":["ISTA Thesis"],"title":"Pathogenic Escherichia coli hijack the host immune response","publication_status":"published","date_created":"2021-11-18T15:05:06Z","department":[{"_id":"MiSi"},{"_id":"CaGu"},{"_id":"GradSch"}],"article_processing_charge":"No","ddc":["570"],"date_updated":"2023-09-07T13:34:38Z","citation":{"ieee":"K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,” Institute of Science and Technology Austria, 2021.","chicago":"Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.” Institute of Science and Technology Austria, 2021. <a href=\"https://doi.org/10.15479/at:ista:10307\">https://doi.org/10.15479/at:ista:10307</a>.","apa":"Tomasek, K. (2021). <i>Pathogenic Escherichia coli hijack the host immune response</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:10307\">https://doi.org/10.15479/at:ista:10307</a>","ama":"Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021. doi:<a href=\"https://doi.org/10.15479/at:ista:10307\">10.15479/at:ista:10307</a>","ista":"Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria.","short":"K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response, Institute of Science and Technology Austria, 2021.","mla":"Tomasek, Kathrin. <i>Pathogenic Escherichia Coli Hijack the Host Immune Response</i>. Institute of Science and Technology Austria, 2021, doi:<a href=\"https://doi.org/10.15479/at:ista:10307\">10.15479/at:ista:10307</a>."},"year":"2021","abstract":[{"text":"Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response.","lang":"eng"}],"doi":"10.15479/at:ista:10307","degree_awarded":"PhD","day":"18"},{"publisher":"Cold Spring Harbor Laboratory","ec_funded":1,"language":[{"iso":"eng"}],"article_processing_charge":"No","project":[{"call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular navigation along spatial gradients","grant_number":"724373"},{"_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P29911","name":"Mechanical adaptation of lamellipodial actin"}],"department":[{"_id":"CaGu"},{"_id":"MiSi"}],"date_created":"2021-11-19T12:24:16Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"publication_status":"submitted","oa_version":"Preprint","month":"10","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","publication":"bioRxiv","_id":"10316","author":[{"id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin","first_name":"Kathrin","last_name":"Tomasek"},{"full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Glatzová","first_name":"Ivana","full_name":"Glatzová, Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d"},{"full_name":"Lukesch, Michael S.","last_name":"Lukesch","first_name":"Michael S."},{"first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-4561-241X","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1"}],"acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S.","status":"public","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","related_material":{"record":[{"status":"public","relation":"later_version","id":"11843"},{"status":"public","relation":"dissertation_contains","id":"10307"}]},"day":"18","doi":"10.1101/2021.10.18.464770","oa":1,"abstract":[{"text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.","lang":"eng"}],"year":"2021","citation":{"mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, <a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>."},"date_updated":"2024-03-25T23:30:19Z","type":"preprint","date_published":"2021-10-18T00:00:00Z"}]