[{"year":"2023","acknowledgement":"We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.).","_id":"13267","month":"08","type":"journal_article","oa_version":"Published Version","date_updated":"2024-01-10T08:37:48Z","abstract":[{"lang":"eng","text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue."}],"page":"1256-1265","date_created":"2023-07-23T22:01:13Z","volume":20,"external_id":{"isi":["001025621500001"],"pmid":["37429995"]},"status":"public","citation":{"short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>.","ieee":"P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>","ista":"Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>"},"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/LIONESS"}],"record":[{"relation":"research_data","id":"12817","status":"public"},{"status":"public","id":"14770","relation":"shorter_version"}]},"intvolume":"        20","publication_status":"published","oa":1,"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"main_file_link":[{"url":"https://doi.org/10.1038/s41592-023-01936-6","open_access":"1"}],"date_published":"2023-08-01T00:00:00Z","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Springer Nature","article_type":"original","scopus_import":"1","article_processing_charge":"Yes","ec_funded":1,"publication":"Nature Methods","day":"01","author":[{"first_name":"Philipp","last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Miguel Villalba, Eder","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder","last_name":"Miguel Villalba"},{"full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","first_name":"Julia M"},{"full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik"},{"full_name":"Wei, Donglai","last_name":"Wei","first_name":"Donglai"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","last_name":"Watson","first_name":"Jake"},{"full_name":"Troidl, Jakob","first_name":"Jakob","last_name":"Troidl"},{"last_name":"Beyer","first_name":"Johanna","full_name":"Beyer, Johanna"},{"last_name":"Ben Simon","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke","first_name":"Wiebke","last_name":"Jahr"},{"first_name":"Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban"},{"full_name":"Broichhagen, Johannes","first_name":"Johannes","last_name":"Broichhagen"},{"full_name":"Grant, Seth G.N.","last_name":"Grant","first_name":"Seth G.N."},{"first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"full_name":"Pfister, Hanspeter","first_name":"Hanspeter","last_name":"Pfister"},{"id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd","last_name":"Bickel","first_name":"Bernd"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","last_name":"Danzl"}],"title":"Dense 4D nanoscale reconstruction of living brain tissue","project":[{"name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385"},{"grant_number":"715767","_id":"24F9549A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635"},{"name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","_id":"2668BFA0-B435-11E9-9278-68D0E5697425","grant_number":"LT00057"}],"language":[{"iso":"eng"}],"isi":1,"publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"quality_controlled":"1","doi":"10.1038/s41592-023-01936-6"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Springer Nature","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"publication":"Nature Biotechnology","article_processing_charge":"Yes (in subscription journal)","scopus_import":"1","ec_funded":1,"article_type":"original","author":[{"first_name":"Julia M","last_name":"Michalska","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia"},{"full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","last_name":"Velicky"},{"full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova","first_name":"Hana"},{"last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823"},{"last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M"},{"orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","first_name":"Nicole","last_name":"Amberg"},{"orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","last_name":"Venturino","first_name":"Alessandro"},{"full_name":"Roessler, Karl","last_name":"Roessler","first_name":"Karl"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"first_name":"Romana","last_name":"Höftberger","full_name":"Höftberger, Romana"},{"first_name":"Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra"},{"first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"},{"first_name":"Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"}],"day":"31","title":"Imaging brain tissue architecture across millimeter to nanometer scales","project":[{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"}],"isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"doi":"10.1038/s41587-023-01911-8","quality_controlled":"1","acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","year":"2023","_id":"14257","date_updated":"2024-02-21T12:18:18Z","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"month":"08","type":"journal_article","oa_version":"Published Version","date_created":"2023-09-03T22:01:15Z","external_id":{"isi":["001065254200001"]},"status":"public","related_material":{"record":[{"id":"13126","status":"public","relation":"research_data"}],"link":[{"url":"https://github.com/danzllab/CATS","relation":"software"}]},"citation":{"short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>.","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>. Springer Nature, 2023.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2023. doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>"},"publication_status":"epub_ahead","oa":1,"date_published":"2023-08-31T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.1038/s41587-023-01911-8","open_access":"1"}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}]},{"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.","year":"2023","_id":"12830","page":"582-596.e7","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."}],"date_updated":"2023-08-01T14:10:38Z","month":"04","type":"journal_article","oa_version":"Published Version","volume":58,"file_date_updated":"2023-04-17T07:41:25Z","date_created":"2023-04-16T22:01:07Z","status":"public","external_id":{"isi":["000982111800001"]},"intvolume":"        58","citation":{"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.","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>.","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.","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>","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>.","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>"},"oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2023-04-10T00:00:00Z","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaHe"},{"_id":"Bio"}],"publication":"Developmental Cell","scopus_import":"1","article_processing_charge":"Yes (via OA deal)","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","author":[{"id":"44C6F6A6-F248-11E8-B48F-1D18A9856A87","full_name":"Huljev, Karla","last_name":"Huljev","first_name":"Karla"},{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","full_name":"Shamipour, Shayan","last_name":"Shamipour","first_name":"Shayan"},{"orcid":"0000-0003-4333-7503","id":"2E839F16-F248-11E8-B48F-1D18A9856A87","full_name":"Nunes Pinheiro, Diana C","first_name":"Diana C","last_name":"Nunes Pinheiro"},{"full_name":"Preusser, Friedrich","first_name":"Friedrich","last_name":"Preusser"},{"last_name":"Steccari","first_name":"Irene","full_name":"Steccari, Irene","id":"2705C766-9FE2-11EA-B224-C6773DDC885E"},{"last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M"},{"id":"2C0B105C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8421-5508","full_name":"Naik, Suyash","first_name":"Suyash","last_name":"Naik"},{"full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","last_name":"Heisenberg"}],"file":[{"date_created":"2023-04-17T07:41:25Z","access_level":"open_access","file_id":"12842","date_updated":"2023-04-17T07:41:25Z","checksum":"c80ca2ebc241232aacdb5aa4b4c80957","file_size":7925886,"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_name":"2023_DevelopmentalCell_Huljev.pdf","success":1}],"day":"10","title":"A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish","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"},{"_id":"26520D1E-B435-11E9-9278-68D0E5697425","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation","grant_number":"ALTF 850-2017"},{"grant_number":"LT000429","name":"Coordination of mesendoderm fate specification and internalization during zebrafish gastrulation","_id":"266BC5CE-B435-11E9-9278-68D0E5697425"}],"isi":1,"language":[{"iso":"eng"}],"issue":"7","publication_identifier":{"issn":["1534-5807"],"eissn":["1878-1551"]},"doi":"10.1016/j.devcel.2023.02.016","quality_controlled":"1"},{"has_accepted_license":"1","publication_status":"published","oa":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"date_published":"2022-07-07T00:00:00Z","ddc":["570"],"status":"public","citation":{"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>","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.","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>.","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>","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).","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>.","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."},"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12726"},{"status":"public","id":"14530","relation":"dissertation_contains"}]},"intvolume":"         1","date_updated":"2023-11-30T10:55:12Z","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"}],"oa_version":"Published Version","month":"07","type":"journal_article","file_date_updated":"2023-08-16T08:00:30Z","date_created":"2022-02-25T07:52:11Z","volume":1,"year":"2022","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.","_id":"10791","publication_identifier":{"eissn":["2753-149X"]},"quality_controlled":"1","doi":"10.1093/oons/kvac009","project":[{"grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812"}],"language":[{"iso":"eng"}],"issue":"1","file":[{"checksum":"822e76e056c07099d1fb27d1ece5941b","date_updated":"2023-08-16T08:00:30Z","file_id":"14061","access_level":"open_access","date_created":"2023-08-16T08:00:30Z","success":1,"file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","creator":"dernst","relation":"main_file","content_type":"application/pdf","file_size":4846551}],"day":"07","author":[{"last_name":"Hansen","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H"},{"last_name":"Pauler","first_name":"Florian","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian"},{"full_name":"Riedl, Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4844-6311","first_name":"Michael","last_name":"Riedl"},{"full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","first_name":"Carmen"},{"last_name":"Heger","first_name":"Anna-Magdalena","full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","first_name":"Susanne","last_name":"Laukoter"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M"},{"first_name":"Armel","last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel"},{"full_name":"Hof, Björn","id":"3A374330-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2057-2754","first_name":"Björn","last_name":"Hof"},{"full_name":"Tsai, Li Huei","first_name":"Li Huei","last_name":"Tsai"},{"last_name":"Rülicke","first_name":"Thomas","full_name":"Rülicke, Thomas"},{"first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","article_number":"kvac009","department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"publisher":"Oxford Academic","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ec_funded":1,"article_processing_charge":"No","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Oxford Open Neuroscience"},{"publication_identifier":{"issn":["2211-1247"]},"quality_controlled":"1","doi":"10.1016/j.celrep.2022.110615","project":[{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"grant_number":"I04205","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"language":[{"iso":"eng"}],"issue":"1","isi":1,"keyword":["General Biochemistry","Genetics and Molecular Biology"],"file":[{"success":1,"file_name":"2022_CellReports_Villa.pdf","content_type":"application/pdf","relation":"main_file","file_size":"7808644","creator":"dernst","date_updated":"2022-04-15T09:06:25Z","file_id":"11164","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","date_created":"2022-04-15T09:06:25Z","access_level":"open_access"}],"day":"05","author":[{"full_name":"Villa, Carlo Emanuele","last_name":"Villa","first_name":"Carlo Emanuele"},{"full_name":"Cheroni, Cristina","first_name":"Cristina","last_name":"Cheroni"},{"last_name":"Dotter","first_name":"Christoph","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"López-Tóbon","first_name":"Alejandro","full_name":"López-Tóbon, Alejandro"},{"id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","last_name":"Oliveira","first_name":"Bárbara"},{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","full_name":"Sacco, Roberto","last_name":"Sacco","first_name":"Roberto"},{"full_name":"Yahya, Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","last_name":"Yahya","first_name":"Aysan Çerağ"},{"first_name":"Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"full_name":"Gabriele, Michele","last_name":"Gabriele","first_name":"Michele"},{"last_name":"Tavakoli","first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854","full_name":"Tavakoli, Mojtaba"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"last_name":"Gabitto","first_name":"Mariano","full_name":"Gabitto, Mariano"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","last_name":"Danzl","first_name":"Johann G"},{"last_name":"Testa","first_name":"Giuseppe","full_name":"Testa, Giuseppe"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","article_number":"110615","pmid":1,"department":[{"_id":"JoDa"},{"_id":"GaNo"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publisher":"Elsevier","article_processing_charge":"Yes","ec_funded":1,"article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Cell Reports","has_accepted_license":"1","publication_status":"published","oa":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"date_published":"2022-04-05T00:00:00Z","ddc":["570"],"external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"status":"public","citation":{"ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>.","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>","ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022.","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>.","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022)."},"intvolume":"        39","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12364"}]},"date_updated":"2024-03-25T23:30:25Z","abstract":[{"text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","month":"04","file_date_updated":"2022-04-15T09:06:25Z","date_created":"2022-04-15T09:03:10Z","volume":39,"year":"2022","acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","_id":"11160"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","scopus_import":"1","ec_funded":1,"article_processing_charge":"No","publication":"Nature Communications","department":[{"_id":"MaLo"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer Nature","article_number":"2635","title":"In vitro reconstitution of Escherichia coli divisome activation","day":"12","file":[{"success":1,"file_name":"2022_NatureCommunications_Radler.pdf","content_type":"application/pdf","relation":"main_file","file_size":6945191,"creator":"dernst","date_updated":"2022-05-13T09:10:51Z","file_id":"11374","checksum":"5af863ee1b95a0710f6ee864d68dc7a6","date_created":"2022-05-13T09:10:51Z","access_level":"open_access"}],"author":[{"full_name":"Radler, Philipp","id":"40136C2A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9198-2182 ","last_name":"Radler","first_name":"Philipp"},{"full_name":"Baranova, Natalia S.","orcid":"0000-0002-3086-9124","id":"38661662-F248-11E8-B48F-1D18A9856A87","first_name":"Natalia S.","last_name":"Baranova"},{"first_name":"Paulo R","last_name":"Dos Santos Caldas","full_name":"Dos Santos Caldas, Paulo R","orcid":"0000-0001-6730-4461","id":"38FCDB4C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","last_name":"Sommer","first_name":"Christoph M"},{"first_name":"Maria D","last_name":"Lopez Pelegrin","id":"319AA9CE-F248-11E8-B48F-1D18A9856A87","full_name":"Lopez Pelegrin, Maria D"},{"last_name":"Michalik","first_name":"David","id":"B9577E20-AA38-11E9-AC9A-0930E6697425","full_name":"Michalik, David"},{"full_name":"Loose, Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724","last_name":"Loose","first_name":"Martin"}],"language":[{"iso":"eng"}],"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry"],"isi":1,"project":[{"name":"Self-Organization of the Bacterial Cell","_id":"2595697A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"679239"},{"grant_number":"P34607","_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d","name":"Understanding bacterial cell division by in vitro\r\nreconstitution"}],"quality_controlled":"1","doi":"10.1038/s41467-022-30301-y","publication_identifier":{"issn":["2041-1723"]},"_id":"11373","year":"2022","acknowledgement":"We acknowledge members of the Loose laboratory at IST Austria for helpful discussions—in particular L. Lindorfer for his assistance with cloning and purifications. We thank J. Löwe and T. Nierhaus (MRC-LMB Cambridge, UK) for sharing unpublished work and helpful discussions, as well as D. Vavylonis and D. Rutkowski (Lehigh University, Bethlehem, PA, USA) and S. Martin (University of Lausanne, Switzerland) for sharing their code for FRAP analysis. We are also thankful for the support by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF). This work was supported by the European Research Council through grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4 to N.B. For the purpose of open access, we have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","date_created":"2022-05-13T09:06:28Z","file_date_updated":"2022-05-13T09:10:51Z","volume":13,"month":"05","oa_version":"Published Version","type":"journal_article","abstract":[{"text":"The actin-homologue FtsA is essential for E. coli cell division, as it links FtsZ filaments in the Z-ring to transmembrane proteins. FtsA is thought to initiate cell constriction by switching from an inactive polymeric to an active monomeric conformation, which recruits downstream proteins and stabilizes the Z-ring. However, direct biochemical evidence for this mechanism is missing. Here, we use reconstitution experiments and quantitative fluorescence microscopy to study divisome activation in vitro. By comparing wild-type FtsA with FtsA R286W, we find that this hyperactive mutant outperforms FtsA WT in replicating FtsZ treadmilling dynamics, FtsZ filament stabilization and recruitment of FtsN. We could attribute these differences to a faster exchange and denser packing of FtsA R286W below FtsZ filaments. Using FRET microscopy, we also find that FtsN binding promotes FtsA self-interaction. We propose that in the active divisome FtsA and FtsN exist as a dynamic copolymer that follows treadmilling filaments of FtsZ.","lang":"eng"}],"date_updated":"2024-02-21T12:35:18Z","citation":{"chicago":"Radler, Philipp, Natalia S. Baranova, Paulo R Dos Santos Caldas, Christoph M Sommer, Maria D Lopez Pelegrin, David Michalik, and Martin Loose. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-30301-y\">https://doi.org/10.1038/s41467-022-30301-y</a>.","ieee":"P. Radler <i>et al.</i>, “In vitro reconstitution of Escherichia coli divisome activation,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","short":"P. Radler, N.S. Baranova, P.R. Dos Santos Caldas, C.M. Sommer, M.D. Lopez Pelegrin, D. Michalik, M. Loose, Nature Communications 13 (2022).","ama":"Radler P, Baranova NS, Dos Santos Caldas PR, et al. In vitro reconstitution of Escherichia coli divisome activation. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-30301-y\">10.1038/s41467-022-30301-y</a>","apa":"Radler, P., Baranova, N. S., Dos Santos Caldas, P. R., Sommer, C. M., Lopez Pelegrin, M. D., Michalik, D., &#38; Loose, M. (2022). In vitro reconstitution of Escherichia coli divisome activation. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-30301-y\">https://doi.org/10.1038/s41467-022-30301-y</a>","mla":"Radler, Philipp, et al. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” <i>Nature Communications</i>, vol. 13, 2635, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-30301-y\">10.1038/s41467-022-30301-y</a>.","ista":"Radler P, Baranova NS, Dos Santos Caldas PR, Sommer CM, Lopez Pelegrin MD, Michalik D, Loose M. 2022. In vitro reconstitution of Escherichia coli divisome activation. Nature Communications. 13, 2635."},"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"14280"},{"id":"10934","status":"public","relation":"research_data"}],"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41467-022-34485-1"}]},"intvolume":"        13","external_id":{"isi":["000795171100037"]},"status":"public","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"date_published":"2022-05-12T00:00:00Z","ddc":["570"],"has_accepted_license":"1","oa":1,"publication_status":"published"},{"title":"Saturated reconstruction of living brain tissue","date_created":"2022-08-23T11:07:59Z","author":[{"last_name":"Velicky","first_name":"Philipp","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Eder","last_name":"Miguel Villalba","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","full_name":"Miguel Villalba, Eder"},{"first_name":"Julia M","last_name":"Michalska","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235"},{"last_name":"Wei","first_name":"Donglai","full_name":"Wei, Donglai"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","last_name":"Watson","first_name":"Jake"},{"full_name":"Troidl, Jakob","first_name":"Jakob","last_name":"Troidl"},{"full_name":"Beyer, Johanna","first_name":"Johanna","last_name":"Beyer"},{"last_name":"Ben Simon","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav"},{"full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer"},{"full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","last_name":"Jahr"},{"last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban"},{"last_name":"Broichhagen","first_name":"Johannes","full_name":"Broichhagen, Johannes"},{"full_name":"Grant, Seth G. N.","last_name":"Grant","first_name":"Seth G. N."},{"orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"},{"full_name":"Pfister, Hanspeter","first_name":"Hanspeter","last_name":"Pfister"},{"first_name":"Bernd","last_name":"Bickel","full_name":"Bickel, Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385"},{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"}],"oa_version":"Preprint","type":"preprint","month":"05","day":"09","date_updated":"2024-03-25T23:30:11Z","abstract":[{"lang":"eng","text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full <jats:italic>in-silico</jats:italic> reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches<jats:sup>6–12</jats:sup> facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy<jats:sup>6,13</jats:sup> in extracellularly labelled tissue<jats:sup>14</jats:sup> for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue."}],"_id":"11943","publication":"bioRxiv","article_processing_charge":"No","publisher":"Cold Spring Harbor Laboratory","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"year":"2022","date_published":"2022-05-09T00:00:00Z","doi":"10.1101/2022.03.16.484431","main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"publication_status":"submitted","oa":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12470"}]},"language":[{"iso":"eng"}],"citation":{"short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.).","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>.","ieee":"P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>","ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, <a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>"},"status":"public"},{"publication_status":"submitted","oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"doi":"10.1101/2022.08.17.504272","date_published":"2022-08-18T00:00:00Z","status":"public","language":[{"iso":"eng"}],"citation":{"short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.).","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>.","ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, <a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>"},"related_material":{"record":[{"status":"public","id":"12470","relation":"dissertation_contains"}]},"month":"08","type":"preprint","oa_version":"Preprint","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons.","lang":"eng"}],"date_updated":"2024-03-25T23:30:11Z","day":"18","author":[{"first_name":"Julia M","last_name":"Michalska","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235"},{"full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik"},{"last_name":"Velicky","first_name":"Philipp","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431"},{"last_name":"Korinkova","first_name":"Hana","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Roessler, Karl","first_name":"Karl","last_name":"Roessler"},{"full_name":"Czech, Thomas","last_name":"Czech","first_name":"Thomas"},{"last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl"}],"date_created":"2022-08-24T08:24:52Z","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Cold Spring Harbor Laboratory","article_processing_charge":"No","_id":"11950","publication":"bioRxiv"},{"project":[{"grant_number":"I03630","name":"Molecular mechanisms of endocytic cargo recognition in plants","call_identifier":"FWF","_id":"26538374-B435-11E9-9278-68D0E5697425"}],"language":[{"iso":"eng"}],"issue":"10","isi":1,"keyword":["Plant Science","Molecular Biology"],"publication_identifier":{"issn":["1674-2052"]},"quality_controlled":"1","doi":"10.1016/j.molp.2022.09.003","pmid":1,"department":[{"_id":"JiFr"},{"_id":"EM-Fac"},{"_id":"Bio"}],"publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","scopus_import":"1","article_processing_charge":"Yes (via OA deal)","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Molecular Plant","day":"03","file":[{"creator":"dernst","file_size":2307251,"relation":"main_file","content_type":"application/pdf","file_name":"2022_MolecularPlant_Johnson.pdf","success":1,"access_level":"open_access","date_created":"2023-01-30T07:46:51Z","checksum":"04d5c12490052d03e4dc4412338a43dd","file_id":"12435","date_updated":"2023-01-30T07:46:51Z"}],"author":[{"id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2739-8843","full_name":"Johnson, Alexander J","first_name":"Alexander J","last_name":"Johnson"},{"full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","last_name":"Kaufmann","first_name":"Walter"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M"},{"last_name":"Costanzo","first_name":"Tommaso","full_name":"Costanzo, Tommaso","orcid":"0000-0001-9732-3815","id":"D93824F4-D9BA-11E9-BB12-F207E6697425"},{"full_name":"Dahhan, Dana A.","last_name":"Dahhan","first_name":"Dana A."},{"full_name":"Bednarek, Sebastian Y.","first_name":"Sebastian Y.","last_name":"Bednarek"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","first_name":"Jiří","last_name":"Friml"}],"title":"Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution","external_id":{"pmid":["36081349"],"isi":["000882769800009"]},"status":"public","citation":{"ama":"Johnson AJ, Kaufmann W, Sommer CM, et al. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. <i>Molecular Plant</i>. 2022;15(10):1533-1542. doi:<a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">10.1016/j.molp.2022.09.003</a>","ista":"Johnson AJ, Kaufmann W, Sommer CM, Costanzo T, Dahhan DA, Bednarek SY, Friml J. 2022. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. Molecular Plant. 15(10), 1533–1542.","mla":"Johnson, Alexander J., et al. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” <i>Molecular Plant</i>, vol. 15, no. 10, Elsevier, 2022, pp. 1533–42, doi:<a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">10.1016/j.molp.2022.09.003</a>.","apa":"Johnson, A. J., Kaufmann, W., Sommer, C. M., Costanzo, T., Dahhan, D. A., Bednarek, S. Y., &#38; Friml, J. (2022). Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. <i>Molecular Plant</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">https://doi.org/10.1016/j.molp.2022.09.003</a>","ieee":"A. J. Johnson <i>et al.</i>, “Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution,” <i>Molecular Plant</i>, vol. 15, no. 10. Elsevier, pp. 1533–1542, 2022.","chicago":"Johnson, Alexander J, Walter Kaufmann, Christoph M Sommer, Tommaso Costanzo, Dana A. Dahhan, Sebastian Y. Bednarek, and Jiří Friml. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” <i>Molecular Plant</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.molp.2022.09.003\">https://doi.org/10.1016/j.molp.2022.09.003</a>.","short":"A.J. Johnson, W. Kaufmann, C.M. Sommer, T. Costanzo, D.A. Dahhan, S.Y. Bednarek, J. Friml, Molecular Plant 15 (2022) 1533–1542."},"intvolume":"        15","has_accepted_license":"1","oa":1,"publication_status":"published","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"Bio"}],"date_published":"2022-10-03T00:00:00Z","ddc":["580"],"year":"2022","acknowledgement":"A.J. is supported by funding from the Austrian Science Fund I3630B25 (to J.F.). This research was supported by the Scientific Service Units of Institute of Science and Technology Austria (ISTA) through resources provided by the Electron Microscopy Facility, Lab Support Facility, and the Imaging and Optics Facility. We acknowledge Prof. David Robinson (Heidelberg) and Prof. Jan Traas (Lyon) for making us aware of previously published classical on-grid preparation methods. No conflict of interest declared.","_id":"12239","date_updated":"2023-08-04T09:39:24Z","abstract":[{"text":"Biological systems are the sum of their dynamic three-dimensional (3D) parts. Therefore, it is critical to study biological structures in 3D and at high resolution to gain insights into their physiological functions. Electron microscopy of metal replicas of unroofed cells and isolated organelles has been a key technique to visualize intracellular structures at nanometer resolution. However, many of these methods require specialized equipment and personnel to complete them. Here, we present novel accessible methods to analyze biological structures in unroofed cells and biochemically isolated organelles in 3D and at nanometer resolution, focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential trafficking organelles, their detailed structural information is lacking due to their poor preservation when observed via classical electron microscopy protocols experiments. First, we establish a method to visualize CCVs in unroofed cells using scanning transmission electron microscopy tomography, providing sufficient resolution to define the clathrin coat arrangements. Critically, the samples are prepared directly on electron microscopy grids, removing the requirement to use extremely corrosive acids, thereby enabling the use of this method in any electron microscopy lab. Secondly, we demonstrate that this standardized sample preparation allows the direct comparison of isolated CCV samples with those visualized in cells. Finally, to facilitate the high-throughput and robust screening of metal replicated samples, we provide a deep learning analysis method to screen the “pseudo 3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes accessible ways to examine the 3D structure of biological samples and provide novel insights into the structure of plant CCVs.","lang":"eng"}],"type":"journal_article","month":"10","oa_version":"Published Version","page":"1533-1542","date_created":"2023-01-16T09:51:49Z","file_date_updated":"2023-01-30T07:46:51Z","volume":15},{"acknowledged_ssus":[{"_id":"PreCl"}],"ddc":["572"],"date_published":"2021-05-24T00:00:00Z","has_accepted_license":"1","oa":1,"publication_status":"published","citation":{"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.","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).","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>","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.","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>."},"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"},{"id":"12401","status":"public","relation":"dissertation_contains"}]},"intvolume":"        12","external_id":{"isi":["000658769900010"]},"status":"public","date_created":"2021-05-28T11:49:46Z","file_date_updated":"2021-05-28T12:39:43Z","volume":12,"date_updated":"2024-09-10T12:04:26Z","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."}],"month":"05","type":"journal_article","oa_version":"Published Version","_id":"9429","year":"2021","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).","quality_controlled":"1","doi":"10.1038/s41467-021-23123-x","publication_identifier":{"eissn":["2041-1723"]},"language":[{"iso":"eng"}],"issue":"1","isi":1,"keyword":["General Biochemistry","Genetics and Molecular Biology"],"project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"},{"name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F07807"},{"grant_number":"I03600","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules"}],"title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","article_number":"3058","file":[{"file_name":"2021_NatureCommunications_Morandell.pdf","success":1,"creator":"kschuh","file_size":9358599,"relation":"main_file","content_type":"application/pdf","checksum":"337e0f7959c35ec959984cacdcb472ba","file_id":"9430","date_updated":"2021-05-28T12:39:43Z","access_level":"open_access","date_created":"2021-05-28T12:39:43Z"}],"day":"24","author":[{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","first_name":"Jasmin","last_name":"Morandell"},{"last_name":"Schwarz","first_name":"Lena A","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette","last_name":"Basilico"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","last_name":"Tasciyan","first_name":"Saren"},{"id":"38C393BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8370-6161","full_name":"Dimchev, Georgi A","first_name":"Georgi A","last_name":"Dimchev"},{"last_name":"Nicolas","first_name":"Armel","full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","first_name":"Caroline","last_name":"Kreuzinger"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","first_name":"Christoph","last_name":"Dotter"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","first_name":"Lisa","last_name":"Knaus"},{"first_name":"Zoe","last_name":"Dobler","full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F"},{"last_name":"Cacci","first_name":"Emanuele","full_name":"Cacci, Emanuele"},{"last_name":"Schur","first_name":"Florian KM","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078"},{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia"}],"ec_funded":1,"article_processing_charge":"No","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Nature Communications","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"publisher":"Springer Nature","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"doi":"10.15252/embj.2021108714","quality_controlled":"1","publication_identifier":{"issn":["0261-4189"],"eissn":["1460-2075"]},"isi":1,"language":[{"iso":"eng"}],"issue":"23","title":"Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration","article_number":"e108714","author":[{"full_name":"Bajaj, Sunanjay","first_name":"Sunanjay","last_name":"Bajaj"},{"last_name":"Bagley","first_name":"Joshua A.","full_name":"Bagley, Joshua A."},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer"},{"first_name":"Abel","last_name":"Vertesy","full_name":"Vertesy, Abel"},{"full_name":"Nagumo Wong, Sakurako","last_name":"Nagumo Wong","first_name":"Sakurako"},{"full_name":"Krenn, Veronica","last_name":"Krenn","first_name":"Veronica"},{"last_name":"Lévi-Strauss","first_name":"Julie","full_name":"Lévi-Strauss, Julie"},{"full_name":"Knoblich, Juergen A.","first_name":"Juergen A.","last_name":"Knoblich"}],"file":[{"file_name":"2021_EMBO_Bajaj.pdf","success":1,"creator":"alisjak","file_size":7819881,"relation":"main_file","content_type":"application/pdf","checksum":"78d2d02e775322297e774f72810a41a4","file_id":"10541","date_updated":"2021-12-13T14:54:14Z","access_level":"open_access","date_created":"2021-12-13T14:54:14Z"}],"day":"18","publication":"EMBO Journal","scopus_import":"1","article_processing_charge":"Yes (in subscription journal)","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publisher":"Embo Press","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"department":[{"_id":"Bio"}],"date_published":"2021-10-18T00:00:00Z","ddc":["610"],"oa":1,"publication_status":"published","has_accepted_license":"1","intvolume":"        40","citation":{"chicago":"Bajaj, Sunanjay, Joshua A. Bagley, Christoph M Sommer, Abel Vertesy, Sakurako Nagumo Wong, Veronica Krenn, Julie Lévi-Strauss, and Juergen A. Knoblich. “Neurotransmitter Signaling Regulates Distinct Phases of Multimodal Human Interneuron Migration.” <i>EMBO Journal</i>. Embo Press, 2021. <a href=\"https://doi.org/10.15252/embj.2021108714\">https://doi.org/10.15252/embj.2021108714</a>.","ieee":"S. Bajaj <i>et al.</i>, “Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration,” <i>EMBO Journal</i>, vol. 40, no. 23. Embo Press, 2021.","short":"S. Bajaj, J.A. Bagley, C.M. Sommer, A. Vertesy, S. Nagumo Wong, V. Krenn, J. Lévi-Strauss, J.A. Knoblich, EMBO Journal 40 (2021).","ama":"Bajaj S, Bagley JA, Sommer CM, et al. Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. <i>EMBO Journal</i>. 2021;40(23). doi:<a href=\"https://doi.org/10.15252/embj.2021108714\">10.15252/embj.2021108714</a>","apa":"Bajaj, S., Bagley, J. A., Sommer, C. M., Vertesy, A., Nagumo Wong, S., Krenn, V., … Knoblich, J. A. (2021). Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. <i>EMBO Journal</i>. Embo Press. <a href=\"https://doi.org/10.15252/embj.2021108714\">https://doi.org/10.15252/embj.2021108714</a>","ista":"Bajaj S, Bagley JA, Sommer CM, Vertesy A, Nagumo Wong S, Krenn V, Lévi-Strauss J, Knoblich JA. 2021. Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. EMBO Journal. 40(23), e108714.","mla":"Bajaj, Sunanjay, et al. “Neurotransmitter Signaling Regulates Distinct Phases of Multimodal Human Interneuron Migration.” <i>EMBO Journal</i>, vol. 40, no. 23, e108714, Embo Press, 2021, doi:<a href=\"https://doi.org/10.15252/embj.2021108714\">10.15252/embj.2021108714</a>."},"external_id":{"isi":["000708012800001"],"pmid":["34661293"]},"status":"public","volume":40,"file_date_updated":"2021-12-13T14:54:14Z","date_created":"2021-10-24T22:01:34Z","abstract":[{"text":"Inhibitory GABAergic interneurons migrate over long distances from their extracortical origin into the developing cortex. In humans, this process is uniquely slow and prolonged, and it is unclear whether guidance cues unique to humans govern the various phases of this complex developmental process. Here, we use fused cerebral organoids to identify key roles of neurotransmitter signaling pathways in guiding the migratory behavior of human cortical interneurons. We use scRNAseq to reveal expression of GABA, glutamate, glycine, and serotonin receptors along distinct maturation trajectories across interneuron migration. We develop an image analysis software package, TrackPal, to simultaneously assess 48 parameters for entire migration tracks of individual cells. By chemical screening, we show that different modes of interneuron migration depend on distinct neurotransmitter signaling pathways, linking transcriptional maturation of interneurons with their migratory behavior. Altogether, our study provides a comprehensive quantitative analysis of human interneuron migration and its functional modulation by neurotransmitter signaling.","lang":"eng"}],"date_updated":"2023-08-14T08:05:23Z","type":"journal_article","month":"10","oa_version":"Published Version","_id":"10179","acknowledgement":"We thank all Knoblich laboratory members for continued support and discussions. We thank the IMP/IMBA BioOptics facility, particularly Pawel Pasierbek, Alberto Moreno Cencerrado and Gerald Schmauss, the IMP/IMBA Molecular Biology Service, in particular Robert Heinen, the IMP Bioinformatics facility, in particular Thomas Burkard, the Vienna Biocenter Core Facilities (VBCF) Histopathology facility, in particular Tamara Engelmaier, and the VBCF Next Generation Sequencing Facility, notably Volodymyr Shubchynskyy and Carmen Czepe. We would also like to thank Simon Haendeler for advice on statistical analyses, Jose Guzman for discussions and assistance with slice culture setups, Oliver L. Eichmueller for discussions and assistance with microscopy, and E.H. Gustafson, S. Wolfinger, and D. Reumann for technical assistance regarding generation of cerebral organoids. This project received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie fellowship agreement Nr.707109 awarded to J.A.B. Work in J.A.K.'s laboratory is supported by the Austrian Federal Ministry of Education, Science and Research, the Austrian Academy of Sciences, the City of Vienna, a Research Program of the Austrian Science Fund FWF (SFBF78 Stem Cell, F 7803-B) and a European Research Council (ERC) Advanced Grant under the European 20 Union’s Horizon 2020 program (grant agreement no. 695642).","year":"2021"},{"doi":"10.1101/2020.01.10.902064 ","language":[{"iso":"eng"}],"project":[{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets"}],"title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","day":"11","file":[{"content_type":"application/pdf","relation":"main_file","file_size":2931370,"creator":"rsix","file_name":"2020.01.10.902064v1.full.pdf","date_created":"2020-05-05T14:31:19Z","access_level":"open_access","date_updated":"2020-07-14T12:48:03Z","file_id":"7801","checksum":"c6799ab5daba80efe8e2ed63c15f8c81"}],"author":[{"full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","first_name":"Jasmin"},{"last_name":"Schwarz","first_name":"Lena A","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Basilico","first_name":"Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","full_name":"Basilico, Bernadette"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","last_name":"Tasciyan","first_name":"Saren"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","first_name":"Armel","last_name":"Nicolas"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M"},{"first_name":"Caroline","last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe","first_name":"Zoe","last_name":"Dobler"},{"last_name":"Cacci","first_name":"Emanuele","full_name":"Cacci, Emanuele"},{"first_name":"Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"},{"last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"}],"article_processing_charge":"No","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication":"bioRxiv","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"publisher":"Cold Spring Harbor Laboratory","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledged_ssus":[{"_id":"PreCl"}],"ddc":["570"],"date_published":"2020-01-11T00:00:00Z","has_accepted_license":"1","oa":1,"publication_status":"submitted","citation":{"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>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.)."},"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"8620"},{"relation":"later_version","status":"public","id":"9429"}]},"status":"public","file_date_updated":"2020-07-14T12:48:03Z","date_created":"2020-05-05T14:31:33Z","abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages."}],"date_updated":"2024-09-10T12:04:26Z","oa_version":"Preprint","type":"preprint","month":"01","_id":"7800","year":"2020"},{"publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"MaLo"}],"publication":"Methods in Cell Biology","ec_funded":1,"article_processing_charge":"No","scopus_import":"1","author":[{"full_name":"Dos Santos Caldas, Paulo R","id":"38FCDB4C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6730-4461","last_name":"Dos Santos Caldas","first_name":"Paulo R"},{"orcid":"0000-0001-9198-2182 ","id":"40136C2A-F248-11E8-B48F-1D18A9856A87","full_name":"Radler, Philipp","last_name":"Radler","first_name":"Philipp"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer"},{"last_name":"Loose","first_name":"Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724","full_name":"Loose, Martin"}],"day":"27","title":"Computational analysis of filament polymerization dynamics in cytoskeletal networks","project":[{"name":"Self-Organization of the Bacterial Cell","call_identifier":"H2020","_id":"2595697A-B435-11E9-9278-68D0E5697425","grant_number":"679239"},{"name":"Reconstitution of Bacterial Cell Division Using Purified Components","_id":"260D98C8-B435-11E9-9278-68D0E5697425"}],"isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0091679X"]},"doi":"10.1016/bs.mcb.2020.01.006","quality_controlled":"1","year":"2020","_id":"7572","page":"145-161","oa_version":"Preprint","month":"02","type":"book_chapter","abstract":[{"lang":"eng","text":"The polymerization–depolymerization dynamics of cytoskeletal proteins play essential roles in the self-organization of cytoskeletal structures, in eukaryotic as well as prokaryotic cells. While advances in fluorescence microscopy and in vitro reconstitution experiments have helped to study the dynamic properties of these complex systems, methods that allow to collect and analyze large quantitative datasets of the underlying polymer dynamics are still missing. Here, we present a novel image analysis workflow to study polymerization dynamics of active filaments in a nonbiased, highly automated manner. Using treadmilling filaments of the bacterial tubulin FtsZ as an example, we demonstrate that our method is able to specifically detect, track and analyze growth and shrinkage of polymers, even in dense networks of filaments. We believe that this automated method can facilitate the analysis of a large variety of dynamic cytoskeletal systems, using standard time-lapse movies obtained from experiments in vitro as well as in the living cell. Moreover, we provide scripts implementing this method as supplementary material."}],"date_updated":"2023-10-04T09:50:24Z","volume":158,"date_created":"2020-03-08T23:00:47Z","alternative_title":["Methods in Cell Biology"],"status":"public","external_id":{"isi":["000611826500008"]},"editor":[{"full_name":"Tran, Phong ","first_name":"Phong ","last_name":"Tran"}],"intvolume":"       158","related_material":{"record":[{"status":"public","id":"8358","relation":"part_of_dissertation"}]},"citation":{"ieee":"P. R. Dos Santos Caldas, P. Radler, C. M. Sommer, and M. Loose, “Computational analysis of filament polymerization dynamics in cytoskeletal networks,” in <i>Methods in Cell Biology</i>, vol. 158, P. Tran, Ed. Elsevier, 2020, pp. 145–161.","chicago":"Dos Santos Caldas, Paulo R, Philipp Radler, Christoph M Sommer, and Martin Loose. “Computational Analysis of Filament Polymerization Dynamics in Cytoskeletal Networks.” In <i>Methods in Cell Biology</i>, edited by Phong  Tran, 158:145–61. Elsevier, 2020. <a href=\"https://doi.org/10.1016/bs.mcb.2020.01.006\">https://doi.org/10.1016/bs.mcb.2020.01.006</a>.","short":"P.R. Dos Santos Caldas, P. Radler, C.M. Sommer, M. Loose, in:, P. Tran (Ed.), Methods in Cell Biology, Elsevier, 2020, pp. 145–161.","ama":"Dos Santos Caldas PR, Radler P, Sommer CM, Loose M. Computational analysis of filament polymerization dynamics in cytoskeletal networks. In: Tran P, ed. <i>Methods in Cell Biology</i>. Vol 158. Elsevier; 2020:145-161. doi:<a href=\"https://doi.org/10.1016/bs.mcb.2020.01.006\">10.1016/bs.mcb.2020.01.006</a>","ista":"Dos Santos Caldas PR, Radler P, Sommer CM, Loose M. 2020.Computational analysis of filament polymerization dynamics in cytoskeletal networks. In: Methods in Cell Biology. Methods in Cell Biology, vol. 158, 145–161.","mla":"Dos Santos Caldas, Paulo R., et al. “Computational Analysis of Filament Polymerization Dynamics in Cytoskeletal Networks.” <i>Methods in Cell Biology</i>, edited by Phong  Tran, vol. 158, Elsevier, 2020, pp. 145–61, doi:<a href=\"https://doi.org/10.1016/bs.mcb.2020.01.006\">10.1016/bs.mcb.2020.01.006</a>.","apa":"Dos Santos Caldas, P. R., Radler, P., Sommer, C. M., &#38; Loose, M. (2020). Computational analysis of filament polymerization dynamics in cytoskeletal networks. In P. Tran (Ed.), <i>Methods in Cell Biology</i> (Vol. 158, pp. 145–161). Elsevier. <a href=\"https://doi.org/10.1016/bs.mcb.2020.01.006\">https://doi.org/10.1016/bs.mcb.2020.01.006</a>"},"publication_status":"published","oa":1,"date_published":"2020-02-27T00:00:00Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/839571"}]},{"day":"01","file":[{"checksum":"7efb9951e7ddf3e3dcc2fb92b859c623","file_id":"9619","date_updated":"2021-06-29T14:41:46Z","access_level":"open_access","date_created":"2021-06-29T14:41:46Z","file_name":"181031_Truckenbrodt_ExM_NatProtoc.docx","success":1,"creator":"kschuh","file_size":84478958,"relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"}],"author":[{"full_name":"Truckenbrodt, Sven M","id":"45812BD4-F248-11E8-B48F-1D18A9856A87","last_name":"Truckenbrodt","first_name":"Sven M"},{"first_name":"Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M"},{"last_name":"Rizzoli","first_name":"Silvio O","full_name":"Rizzoli, Silvio O"},{"last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"}],"title":"A practical guide to optimization in X10 expansion microscopy","pmid":1,"department":[{"_id":"JoDa"},{"_id":"Bio"}],"publisher":"Nature Publishing Group","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ec_funded":1,"article_processing_charge":"No","scopus_import":"1","article_type":"original","publication":"Nature Protocols","quality_controlled":"1","doi":"10.1038/s41596-018-0117-3","project":[{"grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships"},{"name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600"}],"language":[{"iso":"eng"}],"issue":"3","isi":1,"date_updated":"2023-08-24T14:48:33Z","abstract":[{"text":"Expansion microscopy is a relatively new approach to super-resolution imaging that uses expandable hydrogels to isotropically increase the physical distance between fluorophores in biological samples such as cell cultures or tissue slices. The classic gel recipe results in an expansion factor of ~4×, with a resolution of 60–80 nm. We have recently developed X10 microscopy, which uses a gel that achieves an expansion factor of ~10×, with a resolution of ~25 nm. Here, we provide a step-by-step protocol for X10 expansion microscopy. A typical experiment consists of seven sequential stages: (i) immunostaining, (ii) anchoring, (iii) polymerization, (iv) homogenization, (v) expansion, (vi) imaging, and (vii) validation. The protocol presented here includes recommendations for optimization, pitfalls and their solutions, and detailed guidelines that should increase reproducibility. Although our protocol focuses on X10 expansion microscopy, we detail which of these suggestions are also applicable to classic fourfold expansion microscopy. We exemplify our protocol using primary hippocampal neurons from rats, but our approach can be used with other primary cells or cultured cell lines of interest. This protocol will enable any researcher with basic experience in immunostainings and access to an epifluorescence microscope to perform super-resolution microscopy with X10. The procedure takes 3 d and requires ~5 h of actively handling the sample for labeling and expansion, and another ~3 h for imaging and analysis.","lang":"eng"}],"month":"03","type":"journal_article","oa_version":"Submitted Version","page":"832–863","file_date_updated":"2021-06-29T14:41:46Z","date_created":"2019-02-24T22:59:20Z","volume":14,"year":"2019","_id":"6052","has_accepted_license":"1","publication_status":"published","oa":1,"ddc":["570"],"date_published":"2019-03-01T00:00:00Z","external_id":{"isi":["000459890700008"],"pmid":["30778205"]},"status":"public","citation":{"chicago":"Truckenbrodt, Sven M, Christoph M Sommer, Silvio O Rizzoli, and Johann G Danzl. “A Practical Guide to Optimization in X10 Expansion Microscopy.” <i>Nature Protocols</i>. Nature Publishing Group, 2019. <a href=\"https://doi.org/10.1038/s41596-018-0117-3\">https://doi.org/10.1038/s41596-018-0117-3</a>.","ieee":"S. M. Truckenbrodt, C. M. Sommer, S. O. Rizzoli, and J. G. Danzl, “A practical guide to optimization in X10 expansion microscopy,” <i>Nature Protocols</i>, vol. 14, no. 3. Nature Publishing Group, pp. 832–863, 2019.","short":"S.M. Truckenbrodt, C.M. Sommer, S.O. Rizzoli, J.G. Danzl, Nature Protocols 14 (2019) 832–863.","ama":"Truckenbrodt SM, Sommer CM, Rizzoli SO, Danzl JG. A practical guide to optimization in X10 expansion microscopy. <i>Nature Protocols</i>. 2019;14(3):832–863. doi:<a href=\"https://doi.org/10.1038/s41596-018-0117-3\">10.1038/s41596-018-0117-3</a>","apa":"Truckenbrodt, S. M., Sommer, C. M., Rizzoli, S. O., &#38; Danzl, J. G. (2019). A practical guide to optimization in X10 expansion microscopy. <i>Nature Protocols</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41596-018-0117-3\">https://doi.org/10.1038/s41596-018-0117-3</a>","mla":"Truckenbrodt, Sven M., et al. “A Practical Guide to Optimization in X10 Expansion Microscopy.” <i>Nature Protocols</i>, vol. 14, no. 3, Nature Publishing Group, 2019, pp. 832–863, doi:<a href=\"https://doi.org/10.1038/s41596-018-0117-3\">10.1038/s41596-018-0117-3</a>.","ista":"Truckenbrodt SM, Sommer CM, Rizzoli SO, Danzl JG. 2019. A practical guide to optimization in X10 expansion microscopy. Nature Protocols. 14(3), 832–863."},"intvolume":"        14"},{"date_created":"2021-08-19T11:49:58Z","title":"Ilastik: Interactive learning and segmentation toolkit","date_updated":"2023-02-23T14:13:38Z","day":"09","abstract":[{"text":"Segmentation is the process of partitioning digital images into meaningful regions. The analysis of biological high content images often requires segmentation as a first step. We propose ilastik as an easy-to-use tool which allows the user without expertise in image processing to perform segmentation and classification in a unified way. ilastik learns from labels provided by the user through a convenient mouse interface. Based on these labels, ilastik infers a problem specific segmentation. A random forest classifier is used in the learning step, in which each pixel's neighborhood is characterized by a set of generic (nonlinear) features. ilastik supports up to three spatial plus one spectral dimension and makes use of all dimensions in the feature calculation. ilastik provides realtime feedback that enables the user to interactively refine the segmentation result and hence further fine-tune the classifier. An uncertainty measure guides the user to ambiguous regions in the images. Real time performance is achieved by multi-threading which fully exploits the capabilities of modern multi-core machines. Once a classifier has been trained on a set of representative images, it can be exported and used to automatically process a very large number of images (e.g. using the CellProfiler pipeline). ilastik is an open source project and released under the BSD license at www.ilastik.org.","lang":"eng"}],"oa_version":"Preprint","type":"conference","month":"06","author":[{"full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer"},{"full_name":"Straehle, Christoph","last_name":"Straehle","first_name":"Christoph"},{"first_name":"Ullrich","last_name":"Köthe","full_name":"Köthe, Ullrich"},{"last_name":"Hamprecht","first_name":"Fred A.","full_name":"Hamprecht, Fred A."}],"article_processing_charge":"No","publication":"2011 IEEE International Symposium on Biomedical Imaging: from Nano to Micro","_id":"9943","year":"2011","department":[{"_id":"Bio"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","publisher":"Institute of Electrical and Electronics Engineers","main_file_link":[{"url":"https://www.researchgate.net/publication/224241106_Ilastik_Interactive_learning_and_segmentation_toolkit","open_access":"1"}],"quality_controlled":"1","date_published":"2011-06-09T00:00:00Z","doi":"10.1109/isbi.2011.5872394","oa":1,"publication_status":"published","publication_identifier":{"issn":["1945-7928"],"eissn":["1945-8452"],"isbn":["978-1-4244-4127-3"]},"citation":{"apa":"Sommer, C. M., Straehle, C., Köthe, U., &#38; Hamprecht, F. A. (2011). Ilastik: Interactive learning and segmentation toolkit. In <i>2011 IEEE International Symposium on Biomedical Imaging: from Nano to Micro</i>. Chicago, Illinois, USA: Institute of Electrical and Electronics Engineers. <a href=\"https://doi.org/10.1109/isbi.2011.5872394\">https://doi.org/10.1109/isbi.2011.5872394</a>","ista":"Sommer CM, Straehle C, Köthe U, Hamprecht FA. 2011. Ilastik: Interactive learning and segmentation toolkit. 2011 IEEE International Symposium on Biomedical Imaging: from Nano to Micro. ISBI: International Symposium on Biomedical Imaging.","mla":"Sommer, Christoph M., et al. “Ilastik: Interactive Learning and Segmentation Toolkit.” <i>2011 IEEE International Symposium on Biomedical Imaging: From Nano to Micro</i>, Institute of Electrical and Electronics Engineers, 2011, doi:<a href=\"https://doi.org/10.1109/isbi.2011.5872394\">10.1109/isbi.2011.5872394</a>.","ama":"Sommer CM, Straehle C, Köthe U, Hamprecht FA. Ilastik: Interactive learning and segmentation toolkit. In: <i>2011 IEEE International Symposium on Biomedical Imaging: From Nano to Micro</i>. Institute of Electrical and Electronics Engineers; 2011. doi:<a href=\"https://doi.org/10.1109/isbi.2011.5872394\">10.1109/isbi.2011.5872394</a>","short":"C.M. Sommer, C. Straehle, U. Köthe, F.A. Hamprecht, in:, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Micro, Institute of Electrical and Electronics Engineers, 2011.","chicago":"Sommer, Christoph M, Christoph Straehle, Ullrich Köthe, and Fred A. Hamprecht. “Ilastik: Interactive Learning and Segmentation Toolkit.” In <i>2011 IEEE International Symposium on Biomedical Imaging: From Nano to Micro</i>. Institute of Electrical and Electronics Engineers, 2011. <a href=\"https://doi.org/10.1109/isbi.2011.5872394\">https://doi.org/10.1109/isbi.2011.5872394</a>.","ieee":"C. M. Sommer, C. Straehle, U. Köthe, and F. A. Hamprecht, “Ilastik: Interactive learning and segmentation toolkit,” in <i>2011 IEEE International Symposium on Biomedical Imaging: from Nano to Micro</i>, Chicago, Illinois, USA, 2011."},"language":[{"iso":"eng"}],"extern":"1","conference":{"end_date":"2011-04-02","start_date":"2011-03-30","location":"Chicago, Illinois, USA","name":"ISBI: International Symposium on Biomedical Imaging"},"keyword":["image segmentation","biomedical imaging","three dimensional displays","neurons","retina","observers","image color analysis"],"status":"public"}]