[{"ddc":["570"],"volume":151,"acknowledgement":"We thank Patrick Müller for sharing the chordintt250 mutant zebrafish line as well as the plasmid for chrd-GFP, Katherine Rogers for sharing the bmp2b plasmid and Andrea Pauli for sharing the draculin plasmid. Diana Pinheiro generated the MZlefty1,2;Tg(sebox::EGFP) line. We are grateful to Patrick Müller, Diana Pinheiro and Katherine Rogers and members of the Heisenberg lab for discussions, technical advice and feedback on the manuscript. We also thank Anna Kicheva and Edouard Hannezo for discussions. We thank the Imaging and Optics Facility as well as the Life Science facility at IST Austria for support with microscopy and fish maintenance.\r\nThis work was supported by a European Research Council Advanced Grant\r\n(MECSPEC 742573 to C.-P.H.). A.S. is a recipient of a DOC Fellowship of the Austrian\r\nAcademy of Sciences at IST Austria. Open Access funding provided by Institute of\r\nScience and Technology Austria. ","abstract":[{"text":"Embryogenesis results from the coordinated activities of different signaling pathways controlling cell fate specification and morphogenesis. In vertebrate gastrulation, both Nodal and BMP signaling play key roles in germ layer specification and morphogenesis, yet their interplay to coordinate embryo patterning with morphogenesis is still insufficiently understood. Here, we took a reductionist approach using zebrafish embryonic explants to study the coordination of Nodal and BMP signaling for embryo patterning and morphogenesis. We show that Nodal signaling triggers explant elongation by inducing mesendodermal progenitors but also suppressing BMP signaling activity at the site of mesendoderm induction. Consistent with this, ectopic BMP signaling in the mesendoderm blocks cell alignment and oriented mesendoderm intercalations, key processes during explant elongation. Translating these ex vivo observations to the intact embryo showed that, similar to explants, Nodal signaling suppresses the effect of BMP signaling on cell intercalations in the dorsal domain, thus allowing robust embryonic axis elongation. These findings suggest a dual function of Nodal signaling in embryonic axis elongation by both inducing mesendoderm and suppressing BMP effects in the dorsal portion of the mesendoderm.","lang":"eng"}],"day":"01","doi":"10.1242/dev.202316","year":"2024","citation":{"ista":"Schauer A, Pranjic-Ferscha K, Hauschild R, Heisenberg C-PJ. 2024. Robust axis elongation by Nodal-dependent restriction of BMP signaling. Development. 151(4), 1–18.","mla":"Schauer, Alexandra, et al. “Robust Axis Elongation by Nodal-Dependent Restriction of BMP Signaling.” <i>Development</i>, vol. 151, no. 4, The Company of Biologists, 2024, pp. 1–18, doi:<a href=\"https://doi.org/10.1242/dev.202316\">10.1242/dev.202316</a>.","short":"A. Schauer, K. Pranjic-Ferscha, R. Hauschild, C.-P.J. Heisenberg, Development 151 (2024) 1–18.","chicago":"Schauer, Alexandra, Kornelija Pranjic-Ferscha, Robert Hauschild, and Carl-Philipp J Heisenberg. “Robust Axis Elongation by Nodal-Dependent Restriction of BMP Signaling.” <i>Development</i>. The Company of Biologists, 2024. <a href=\"https://doi.org/10.1242/dev.202316\">https://doi.org/10.1242/dev.202316</a>.","ieee":"A. Schauer, K. Pranjic-Ferscha, R. Hauschild, and C.-P. J. Heisenberg, “Robust axis elongation by Nodal-dependent restriction of BMP signaling,” <i>Development</i>, vol. 151, no. 4. The Company of Biologists, pp. 1–18, 2024.","ama":"Schauer A, Pranjic-Ferscha K, Hauschild R, Heisenberg C-PJ. Robust axis elongation by Nodal-dependent restriction of BMP signaling. <i>Development</i>. 2024;151(4):1-18. doi:<a href=\"https://doi.org/10.1242/dev.202316\">10.1242/dev.202316</a>","apa":"Schauer, A., Pranjic-Ferscha, K., Hauschild, R., &#38; Heisenberg, C.-P. J. (2024). Robust axis elongation by Nodal-dependent restriction of BMP signaling. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.202316\">https://doi.org/10.1242/dev.202316</a>"},"date_updated":"2024-03-04T07:28:25Z","article_type":"original","publisher":"The Company of Biologists","file_date_updated":"2024-03-04T07:24:43Z","ec_funded":1,"quality_controlled":"1","page":"1-18","intvolume":"       151","title":"Robust axis elongation by Nodal-dependent restriction of BMP signaling","department":[{"_id":"CaHe"},{"_id":"Bio"}],"date_created":"2024-03-03T23:00:50Z","article_processing_charge":"Yes (via OA deal)","publication_status":"published","issue":"4","author":[{"orcid":"0000-0001-7659-9142","full_name":"Schauer, Alexandra","first_name":"Alexandra","last_name":"Schauer","id":"30A536BA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Kornelija","last_name":"Pranjic-Ferscha","full_name":"Pranjic-Ferscha, Kornelija","id":"4362B3C2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","_id":"15048","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"record":[{"id":"14926","relation":"research_data","status":"public"}]},"file":[{"file_size":14839986,"checksum":"6961ea10012bf0d266681f9628bb8f13","date_created":"2024-03-04T07:24:43Z","content_type":"application/pdf","file_name":"2024_Development_Schauer.pdf","date_updated":"2024-03-04T07:24:43Z","success":1,"relation":"main_file","access_level":"open_access","creator":"dernst","file_id":"15050"}],"oa":1,"publication_identifier":{"issn":["0950-1991"],"eissn":["1477-9129"]},"type":"journal_article","date_published":"2024-02-01T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"language":[{"iso":"eng"}],"month":"02","project":[{"_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573"},{"_id":"26B1E39C-B435-11E9-9278-68D0E5697425","grant_number":"25239","name":"Mesendoderm specification in zebrafish: The role of extraembryonic tissues"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"has_accepted_license":"1","publication":"Development"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","file":[{"date_updated":"2024-01-10T12:41:13Z","file_name":"2023_Development_Harish.pdf","content_type":"application/pdf","date_created":"2024-01-10T12:41:13Z","file_size":12836306,"checksum":"2d6f52dc33260a9b2352b8f28374ba5f","file_id":"14790","creator":"dernst","success":1,"relation":"main_file","access_level":"open_access"}],"date_published":"2023-10-01T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"publication_identifier":{"issn":["0950-1991"],"eissn":["1477-9129"]},"language":[{"iso":"eng"}],"keyword":["Developmental Biology","Molecular Biology"],"publication":"Development","has_accepted_license":"1","month":"10","article_number":"dev201559","oa_version":"Published Version","ddc":["570"],"volume":150,"acknowledgement":"We thank members of the Brand lab, as well as Justina Stark (Ivo Sbalzarini group, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany) for project-related discussions; Darren Gilmour (University of Zurich), Karuna Sampath (University of Warwick) and Gokul Kesavan (Vowels Lifesciences Private Limited, Bangalore) for comments on the manuscript; personnel of the CMCB technology platform, TU Dresden for imaging and image analysis-related support; and Maurizio Abbate (Technical support, Arivis) for help with image analysis. We are also grateful to Stapornwongkul and Briscoe for commenting on a preprint version of our work (Stapornwongkul and Briscoe, 2022).\r\nThis work was supported by the Deutsche Forschungsgemeinschaft (BR 1746/6-2, BR 1746/11-1 and BR 1746/3 to M.B.), by a Cluster of Excellence ‘Physics of Life’ seed grant and by institutional funds from Technische Universitat Dresden (to M.B.). Open Access funding provided by Technische Universitat Dresden. Deposited in PMC for immediate release.","isi":1,"external_id":{"isi":["001097449100002"],"pmid":["37665167"]},"date_updated":"2024-01-10T12:45:25Z","year":"2023","citation":{"mla":"Harish, Rohit K., et al. “Real-Time Monitoring of an Endogenous Fgf8a Gradient Attests to Its Role as a Morphogen during Zebrafish Gastrulation.” <i>Development</i>, vol. 150, no. 19, dev201559, The Company of Biologists, 2023, doi:<a href=\"https://doi.org/10.1242/dev.201559\">10.1242/dev.201559</a>.","short":"R.K. Harish, M. Gupta, D. Zöller, H. Hartmann, A. Gheisari, A. Machate, S. Hans, M. Brand, Development 150 (2023).","ista":"Harish RK, Gupta M, Zöller D, Hartmann H, Gheisari A, Machate A, Hans S, Brand M. 2023. Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation. Development. 150(19), dev201559.","ama":"Harish RK, Gupta M, Zöller D, et al. Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation. <i>Development</i>. 2023;150(19). doi:<a href=\"https://doi.org/10.1242/dev.201559\">10.1242/dev.201559</a>","apa":"Harish, R. K., Gupta, M., Zöller, D., Hartmann, H., Gheisari, A., Machate, A., … Brand, M. (2023). Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.201559\">https://doi.org/10.1242/dev.201559</a>","ieee":"R. K. Harish <i>et al.</i>, “Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation,” <i>Development</i>, vol. 150, no. 19. The Company of Biologists, 2023.","chicago":"Harish, Rohit K, Mansi Gupta, Daniela Zöller, Hella Hartmann, Ali Gheisari, Anja Machate, Stefan Hans, and Michael Brand. “Real-Time Monitoring of an Endogenous Fgf8a Gradient Attests to Its Role as a Morphogen during Zebrafish Gastrulation.” <i>Development</i>. The Company of Biologists, 2023. <a href=\"https://doi.org/10.1242/dev.201559\">https://doi.org/10.1242/dev.201559</a>."},"abstract":[{"lang":"eng","text":"Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential."}],"doi":"10.1242/dev.201559","day":"01","file_date_updated":"2024-01-10T12:41:13Z","quality_controlled":"1","article_type":"original","publisher":"The Company of Biologists","author":[{"first_name":"Rohit K","last_name":"Harish","full_name":"Harish, Rohit K","id":"1bae78aa-ee0e-11ec-9b76-bc42990f409d"},{"last_name":"Gupta","first_name":"Mansi","full_name":"Gupta, Mansi"},{"full_name":"Zöller, Daniela","first_name":"Daniela","last_name":"Zöller"},{"last_name":"Hartmann","first_name":"Hella","full_name":"Hartmann, Hella"},{"last_name":"Gheisari","first_name":"Ali","full_name":"Gheisari, Ali"},{"full_name":"Machate, Anja","last_name":"Machate","first_name":"Anja"},{"full_name":"Hans, Stefan","first_name":"Stefan","last_name":"Hans"},{"first_name":"Michael","last_name":"Brand","full_name":"Brand, Michael"}],"issue":"19","pmid":1,"_id":"14774","title":"Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation","intvolume":"       150","publication_status":"published","article_processing_charge":"Yes (via OA deal)","date_created":"2024-01-10T09:18:54Z","department":[{"_id":"AnKi"}]},{"ddc":["570"],"acknowledgement":"iona intestinalis adults were provided by Dr Yutaka Satou (Kyoto University) and Dr Manabu Yoshida (the University of Tokyo) with support from the National Bio-Resource Project of AMED, Japan. We thank Dr Hidehiko Hashimoto and Dr Yuji Mizotani for technical information about 1P-myosin antibody staining. We thank Dr Kaoru Imai and Dr Yutaka Satou for valuable discussion about Admp and for the DNA construct of Bmp2/4 under the Dlx.b upstream sequence. We thank Ms Maki Kogure for constructing the FUSION360 of the intercalating epidermal cell.\r\nThis work was supported by funding from the Japan Society for the Promotion of Science (JP16H01451, JP21H00440). Open Access funding provided by Keio University: Keio Gijuku Daigaku.","volume":149,"external_id":{"pmid":["36227591"],"isi":["000903991700002"]},"isi":1,"citation":{"chicago":"Kogure, Yuki S., Hiromochi Muraoka, Wataru C. Koizumi, Raphaël Gelin-alessi, Benoit G Godard, Kotaro Oka, Carl-Philipp J Heisenberg, and Kohji Hotta. “Admp Regulates Tail Bending by Controlling Ventral Epidermal Cell Polarity via Phosphorylated Myosin Localization in Ciona.” <i>Development</i>. The Company of Biologists, 2022. <a href=\"https://doi.org/10.1242/dev.200215\">https://doi.org/10.1242/dev.200215</a>.","ieee":"Y. S. Kogure <i>et al.</i>, “Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona,” <i>Development</i>, vol. 149, no. 21. The Company of Biologists, 2022.","ama":"Kogure YS, Muraoka H, Koizumi WC, et al. Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona. <i>Development</i>. 2022;149(21). doi:<a href=\"https://doi.org/10.1242/dev.200215\">10.1242/dev.200215</a>","apa":"Kogure, Y. S., Muraoka, H., Koizumi, W. C., Gelin-alessi, R., Godard, B. G., Oka, K., … Hotta, K. (2022). Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.200215\">https://doi.org/10.1242/dev.200215</a>","ista":"Kogure YS, Muraoka H, Koizumi WC, Gelin-alessi R, Godard BG, Oka K, Heisenberg C-PJ, Hotta K. 2022. Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona. Development. 149(21), dev200215.","mla":"Kogure, Yuki S., et al. “Admp Regulates Tail Bending by Controlling Ventral Epidermal Cell Polarity via Phosphorylated Myosin Localization in Ciona.” <i>Development</i>, vol. 149, no. 21, dev200215, The Company of Biologists, 2022, doi:<a href=\"https://doi.org/10.1242/dev.200215\">10.1242/dev.200215</a>.","short":"Y.S. Kogure, H. Muraoka, W.C. Koizumi, R. Gelin-alessi, B.G. Godard, K. Oka, C.-P.J. Heisenberg, K. Hotta, Development 149 (2022)."},"year":"2022","date_updated":"2023-08-04T09:33:24Z","abstract":[{"text":"Ventral tail bending, which is transient but pronounced, is found in many chordate embryos and constitutes an interesting model of how tissue interactions control embryo shape. Here, we identify one key upstream regulator of ventral tail bending in embryos of the ascidian Ciona. We show that during the early tailbud stages, ventral epidermal cells exhibit a boat-shaped morphology (boat cell) with a narrow apical surface where phosphorylated myosin light chain (pMLC) accumulates. We further show that interfering with the function of the BMP ligand Admp led to pMLC localizing to the basal instead of the apical side of ventral epidermal cells and a reduced number of boat cells. Finally, we show that cutting ventral epidermal midline cells at their apex using an ultraviolet laser relaxed ventral tail bending. Based on these results, we propose a previously unreported function for Admp in localizing pMLC to the apical side of ventral epidermal cells, which causes the tail to bend ventrally by resisting antero-posterior notochord extension at the ventral side of the tail.","lang":"eng"}],"day":"01","doi":"10.1242/dev.200215","file_date_updated":"2023-01-27T10:36:50Z","quality_controlled":"1","article_type":"original","publisher":"The Company of Biologists","issue":"21","author":[{"last_name":"Kogure","first_name":"Yuki S.","full_name":"Kogure, Yuki S."},{"last_name":"Muraoka","first_name":"Hiromochi","full_name":"Muraoka, Hiromochi"},{"full_name":"Koizumi, Wataru C.","first_name":"Wataru C.","last_name":"Koizumi"},{"first_name":"Raphaël","last_name":"Gelin-alessi","full_name":"Gelin-alessi, Raphaël"},{"full_name":"Godard, Benoit G","first_name":"Benoit G","last_name":"Godard","id":"3263621A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Kotaro","last_name":"Oka","full_name":"Oka, Kotaro"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","last_name":"Heisenberg"},{"full_name":"Hotta, Kohji","last_name":"Hotta","first_name":"Kohji"}],"scopus_import":"1","_id":"12231","pmid":1,"intvolume":"       149","title":"Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona","department":[{"_id":"CaHe"}],"article_processing_charge":"No","date_created":"2023-01-16T09:50:12Z","publication_status":"published","status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"content_type":"application/pdf","file_name":"2022_Development_Kogure.pdf","date_updated":"2023-01-27T10:36:50Z","file_size":9160451,"checksum":"871b9c58eb79b9e60752de25a46938d6","date_created":"2023-01-27T10:36:50Z","creator":"dernst","file_id":"12423","success":1,"access_level":"open_access","relation":"main_file"}],"type":"journal_article","date_published":"2022-11-01T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"publication_identifier":{"eissn":["1477-9129"],"issn":["0950-1991"]},"keyword":["Developmental Biology","Molecular Biology"],"language":[{"iso":"eng"}],"has_accepted_license":"1","publication":"Development","article_number":"dev200215","month":"11","oa_version":"Published Version"},{"date_published":"2022-10-01T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"publication_identifier":{"eissn":["1477-9129"],"issn":["0950-1991"]},"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","related_material":{"link":[{"relation":"software","url":" https://github.com/burtonjosh/StepwiseMir9"}]},"file":[{"date_created":"2023-01-30T08:35:44Z","checksum":"d7c29b74e9e4032308228cc704a30e88","file_size":9348839,"date_updated":"2023-01-30T08:35:44Z","content_type":"application/pdf","file_name":"2022_Development_Soto.pdf","relation":"main_file","access_level":"open_access","success":1,"file_id":"12438","creator":"dernst"}],"publication":"Development","has_accepted_license":"1","month":"10","article_number":"dev200474","oa_version":"Published Version","language":[{"iso":"eng"}],"keyword":["Developmental Biology","Molecular Biology"],"isi":1,"external_id":{"isi":["000918161000003"],"pmid":["36189829"]},"date_updated":"2023-08-04T09:41:08Z","year":"2022","citation":{"mla":"Soto, Ximena, et al. “Sequential and Additive Expression of MiR-9 Precursors Control Timing of Neurogenesis.” <i>Development</i>, vol. 149, no. 19, dev200474, The Company of Biologists, 2022, doi:<a href=\"https://doi.org/10.1242/dev.200474\">10.1242/dev.200474</a>.","short":"X. Soto, J. Burton, C.S. Manning, T. Minchington, R. Lea, J. Lee, J. Kursawe, M. Rattray, N. Papalopulu, Development 149 (2022).","ista":"Soto X, Burton J, Manning CS, Minchington T, Lea R, Lee J, Kursawe J, Rattray M, Papalopulu N. 2022. Sequential and additive expression of miR-9 precursors control timing of neurogenesis. Development. 149(19), dev200474.","ama":"Soto X, Burton J, Manning CS, et al. Sequential and additive expression of miR-9 precursors control timing of neurogenesis. <i>Development</i>. 2022;149(19). doi:<a href=\"https://doi.org/10.1242/dev.200474\">10.1242/dev.200474</a>","apa":"Soto, X., Burton, J., Manning, C. S., Minchington, T., Lea, R., Lee, J., … Papalopulu, N. (2022). Sequential and additive expression of miR-9 precursors control timing of neurogenesis. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.200474\">https://doi.org/10.1242/dev.200474</a>","ieee":"X. Soto <i>et al.</i>, “Sequential and additive expression of miR-9 precursors control timing of neurogenesis,” <i>Development</i>, vol. 149, no. 19. The Company of Biologists, 2022.","chicago":"Soto, Ximena, Joshua Burton, Cerys S. Manning, Thomas Minchington, Robert Lea, Jessica Lee, Jochen Kursawe, Magnus Rattray, and Nancy Papalopulu. “Sequential and Additive Expression of MiR-9 Precursors Control Timing of Neurogenesis.” <i>Development</i>. The Company of Biologists, 2022. <a href=\"https://doi.org/10.1242/dev.200474\">https://doi.org/10.1242/dev.200474</a>."},"abstract":[{"text":"MicroRNAs (miRs) have an important role in tuning dynamic gene expression. However, the mechanism by which they are quantitatively controlled is unknown. We show that the amount of mature miR-9, a key regulator of neuronal development, increases during zebrafish neurogenesis in a sharp stepwise manner. We characterize the spatiotemporal profile of seven distinct microRNA primary transcripts (pri-mir)-9s that produce the same mature miR-9 and show that they are sequentially expressed during hindbrain neurogenesis. Expression of late-onset pri-mir-9-1 is added on to, rather than replacing, the expression of early onset pri-mir-9-4 and -9-5 in single cells. CRISPR/Cas9 mutation of the late-onset pri-mir-9-1 prevents the developmental increase of mature miR-9, reduces late neuronal differentiation and fails to downregulate Her6 at late stages. Mathematical modelling shows that an adaptive network containing Her6 is insensitive to linear increases in miR-9 but responds to stepwise increases of miR-9. We suggest that a sharp stepwise increase of mature miR-9 is created by sequential and additive temporal activation of distinct loci. This may be a strategy to overcome adaptation and facilitate a transition of Her6 to a new dynamic regime or steady state.","lang":"eng"}],"doi":"10.1242/dev.200474","day":"01","ddc":["570"],"acknowledgement":"We are grateful to Dr Tom Pettini for the advice on smiFISH technique and Dr Laure Bally-Cuif for sharing plasmids. The authors also thank the Biological Services Facility, Bioimaging and Systems Microscopy Facilities of the University of Manchester for technical support.\r\nThis work was supported by a Wellcome Trust Senior Research Fellowship (090868/Z/09/Z) and a Wellcome Trust Investigator Award (224394/Z/21/Z) to N.P. and a Medical Research Council Career Development Award to C.S.M. (MR/V032534/1). J.B. was supported by a Wellcome Trust Four-Year PhD Studentship in Basic Science (219992/Z/19/Z). Open Access funding provided by The University of Manchester. Deposited in PMC for immediate release.","volume":149,"author":[{"first_name":"Ximena","last_name":"Soto","full_name":"Soto, Ximena"},{"full_name":"Burton, Joshua","first_name":"Joshua","last_name":"Burton"},{"full_name":"Manning, Cerys S.","first_name":"Cerys S.","last_name":"Manning"},{"id":"7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f","first_name":"Thomas","last_name":"Minchington","full_name":"Minchington, Thomas"},{"last_name":"Lea","first_name":"Robert","full_name":"Lea, Robert"},{"full_name":"Lee, Jessica","first_name":"Jessica","last_name":"Lee"},{"first_name":"Jochen","last_name":"Kursawe","full_name":"Kursawe, Jochen"},{"first_name":"Magnus","last_name":"Rattray","full_name":"Rattray, Magnus"},{"full_name":"Papalopulu, Nancy","first_name":"Nancy","last_name":"Papalopulu"}],"issue":"19","_id":"12245","pmid":1,"scopus_import":"1","title":"Sequential and additive expression of miR-9 precursors control timing of neurogenesis","intvolume":"       149","publication_status":"published","article_processing_charge":"No","department":[{"_id":"AnKi"}],"date_created":"2023-01-16T09:53:17Z","file_date_updated":"2023-01-30T08:35:44Z","quality_controlled":"1","article_type":"original","publisher":"The Company of Biologists"},{"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1242/dev.176065"}],"oa":1,"publication_identifier":{"eissn":["1477-9129"]},"type":"journal_article","date_published":"2021-02-01T00:00:00Z","language":[{"iso":"eng"}],"article_number":"dev176065","month":"02","project":[{"name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"oa_version":"Published Version","publication":"Development","acknowledgement":"This work was supported in part by the National Science Foundation, through the Center for the Physics of Biological Function (PHY-1734030), by the National Institutes of Health (R01GM097275) and by the Fonds zur Förderung der wissenschaftlichen Forschung (FWF P28844). Deposited in PMC for release after 12 months.","volume":148,"abstract":[{"text":"Half a century after Lewis Wolpert's seminal conceptual advance on how cellular fates distribute in space, we provide a brief historical perspective on how the concept of positional information emerged and influenced the field of developmental biology and beyond. We focus on a modern interpretation of this concept in terms of information theory, largely centered on its application to cell specification in the early Drosophila embryo. We argue that a true physical variable (position) is encoded in local concentrations of patterning molecules, that this mapping is stochastic, and that the processes by which positions and corresponding cell fates are determined based on these concentrations need to take such stochasticity into account. With this approach, we shift the focus from biological mechanisms, molecules, genes and pathways to quantitative systems-level questions: where does positional information reside, how it is transformed and accessed during development, and what fundamental limits it is subject to?","lang":"eng"}],"day":"01","doi":"10.1242/dev.176065","external_id":{"isi":["000613906000007"],"pmid":["33526425"]},"isi":1,"citation":{"apa":"Tkačik, G., &#38; Gregor, T. (2021). The many bits of positional information. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.176065\">https://doi.org/10.1242/dev.176065</a>","ama":"Tkačik G, Gregor T. The many bits of positional information. <i>Development</i>. 2021;148(2). doi:<a href=\"https://doi.org/10.1242/dev.176065\">10.1242/dev.176065</a>","ieee":"G. Tkačik and T. Gregor, “The many bits of positional information,” <i>Development</i>, vol. 148, no. 2. The Company of Biologists, 2021.","chicago":"Tkačik, Gašper, and Thomas Gregor. “The Many Bits of Positional Information.” <i>Development</i>. The Company of Biologists, 2021. <a href=\"https://doi.org/10.1242/dev.176065\">https://doi.org/10.1242/dev.176065</a>.","mla":"Tkačik, Gašper, and Thomas Gregor. “The Many Bits of Positional Information.” <i>Development</i>, vol. 148, no. 2, dev176065, The Company of Biologists, 2021, doi:<a href=\"https://doi.org/10.1242/dev.176065\">10.1242/dev.176065</a>.","short":"G. Tkačik, T. Gregor, Development 148 (2021).","ista":"Tkačik G, Gregor T. 2021. The many bits of positional information. Development. 148(2), dev176065."},"year":"2021","date_updated":"2023-08-07T13:57:30Z","article_type":"original","publisher":"The Company of Biologists","quality_controlled":"1","intvolume":"       148","title":"The many bits of positional information","article_processing_charge":"No","date_created":"2021-03-07T23:01:25Z","department":[{"_id":"GaTk"}],"publication_status":"published","issue":"2","author":[{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik"},{"first_name":"Thomas","last_name":"Gregor","full_name":"Gregor, Thomas"}],"scopus_import":"1","_id":"9226","pmid":1},{"quality_controlled":"1","ec_funded":1,"file_date_updated":"2020-07-14T12:47:50Z","publisher":"The Company of Biologists","article_type":"original","_id":"7165","pmid":1,"scopus_import":"1","author":[{"full_name":"Guerrero, Pilar","first_name":"Pilar","last_name":"Guerrero"},{"last_name":"Perez-Carrasco","first_name":"Ruben","full_name":"Perez-Carrasco, Ruben"},{"full_name":"Zagórski, Marcin P","orcid":"0000-0001-7896-7762","last_name":"Zagórski","first_name":"Marcin P","id":"343DA0DC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Page","first_name":"David","full_name":"Page, David"},{"first_name":"Anna","last_name":"Kicheva","orcid":"0000-0003-4509-4998","full_name":"Kicheva, Anna","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Briscoe, James","first_name":"James","last_name":"Briscoe"},{"first_name":"Karen M.","last_name":"Page","full_name":"Page, Karen M."}],"issue":"23","publication_status":"published","article_processing_charge":"No","date_created":"2019-12-10T14:39:50Z","department":[{"_id":"AnKi"}],"title":"Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium","intvolume":"       146","volume":146,"ddc":["570"],"date_updated":"2023-09-06T11:26:36Z","year":"2019","citation":{"short":"P. Guerrero, R. Perez-Carrasco, M.P. Zagórski, D. Page, A. Kicheva, J. Briscoe, K.M. Page, Development 146 (2019).","mla":"Guerrero, Pilar, et al. “Neuronal Differentiation Influences Progenitor Arrangement in the Vertebrate Neuroepithelium.” <i>Development</i>, vol. 146, no. 23, dev176297, The Company of Biologists, 2019, doi:<a href=\"https://doi.org/10.1242/dev.176297\">10.1242/dev.176297</a>.","ista":"Guerrero P, Perez-Carrasco R, Zagórski MP, Page D, Kicheva A, Briscoe J, Page KM. 2019. Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium. Development. 146(23), dev176297.","ama":"Guerrero P, Perez-Carrasco R, Zagórski MP, et al. Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium. <i>Development</i>. 2019;146(23). doi:<a href=\"https://doi.org/10.1242/dev.176297\">10.1242/dev.176297</a>","apa":"Guerrero, P., Perez-Carrasco, R., Zagórski, M. P., Page, D., Kicheva, A., Briscoe, J., &#38; Page, K. M. (2019). Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.176297\">https://doi.org/10.1242/dev.176297</a>","chicago":"Guerrero, Pilar, Ruben Perez-Carrasco, Marcin P Zagórski, David Page, Anna Kicheva, James Briscoe, and Karen M. Page. “Neuronal Differentiation Influences Progenitor Arrangement in the Vertebrate Neuroepithelium.” <i>Development</i>. The Company of Biologists, 2019. <a href=\"https://doi.org/10.1242/dev.176297\">https://doi.org/10.1242/dev.176297</a>.","ieee":"P. Guerrero <i>et al.</i>, “Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium,” <i>Development</i>, vol. 146, no. 23. The Company of Biologists, 2019."},"isi":1,"external_id":{"pmid":["31784457"],"isi":["000507575700004"]},"doi":"10.1242/dev.176297","day":"04","abstract":[{"lang":"eng","text":"Cell division, movement and differentiation contribute to pattern formation in developing tissues. This is the case in the vertebrate neural tube, in which neurons differentiate in a characteristic pattern from a highly dynamic proliferating pseudostratified epithelium. To investigate how progenitor proliferation and differentiation affect cell arrangement and growth of the neural tube, we used experimental measurements to develop a mechanical model of the apical surface of the neuroepithelium that incorporates the effect of interkinetic nuclear movement and spatially varying rates of neuronal differentiation. Simulations predict that tissue growth and the shape of lineage-related clones of cells differ with the rate of differentiation. Growth is isotropic in regions of high differentiation, but dorsoventrally biased in regions of low differentiation. This is consistent with experimental observations. The absence of directional signalling in the simulations indicates that global mechanical constraints are sufficient to explain the observed differences in anisotropy. This provides insight into how the tissue growth rate affects cell dynamics and growth anisotropy and opens up possibilities to study the coupling between mechanics, pattern formation and growth in the neural tube."}],"language":[{"iso":"eng"}],"publication":"Development","has_accepted_license":"1","oa_version":"Published Version","project":[{"grant_number":"680037","name":"Coordination of Patterning And Growth In the Spinal Cord","_id":"B6FC0238-B512-11E9-945C-1524E6697425","call_identifier":"H2020"}],"month":"12","article_number":"dev176297","file":[{"checksum":"b6533c37dc8fbd803ffeca216e0a8b8a","file_size":7797881,"date_created":"2019-12-13T07:34:06Z","file_name":"2019_Development_Guerrero.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:47:50Z","relation":"main_file","access_level":"open_access","creator":"dernst","file_id":"7177"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2019-12-04T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["0950-1991"],"eissn":["1477-9129"]},"oa":1},{"external_id":{"isi":["000464583200006"],"pmid":["30910826"]},"isi":1,"citation":{"ista":"Stürner T, Tatarnikova A, Müller J, Schaffran B, Cuntz H, Zhang Y, Nemethova M, Bogdan S, Small V, Tavosanis G. 2019. Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo. Development. 146(7), dev171397.","mla":"Stürner, Tomke, et al. “Transient Localization of the Arp2/3 Complex Initiates Neuronal Dendrite Branching in Vivo.” <i>Development</i>, vol. 146, no. 7, dev171397, The Company of Biologists, 2019, doi:<a href=\"https://doi.org/10.1242/dev.171397\">10.1242/dev.171397</a>.","short":"T. Stürner, A. Tatarnikova, J. Müller, B. Schaffran, H. Cuntz, Y. Zhang, M. Nemethova, S. Bogdan, V. Small, G. Tavosanis, Development 146 (2019).","ieee":"T. Stürner <i>et al.</i>, “Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo,” <i>Development</i>, vol. 146, no. 7. The Company of Biologists, 2019.","chicago":"Stürner, Tomke, Anastasia Tatarnikova, Jan Müller, Barbara Schaffran, Hermann Cuntz, Yun Zhang, Maria Nemethova, Sven Bogdan, Vic Small, and Gaia Tavosanis. “Transient Localization of the Arp2/3 Complex Initiates Neuronal Dendrite Branching in Vivo.” <i>Development</i>. The Company of Biologists, 2019. <a href=\"https://doi.org/10.1242/dev.171397\">https://doi.org/10.1242/dev.171397</a>.","apa":"Stürner, T., Tatarnikova, A., Müller, J., Schaffran, B., Cuntz, H., Zhang, Y., … Tavosanis, G. (2019). Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.171397\">https://doi.org/10.1242/dev.171397</a>","ama":"Stürner T, Tatarnikova A, Müller J, et al. Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo. <i>Development</i>. 2019;146(7). doi:<a href=\"https://doi.org/10.1242/dev.171397\">10.1242/dev.171397</a>"},"year":"2019","date_updated":"2023-09-07T14:47:00Z","abstract":[{"lang":"eng","text":"The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neurons, combined with genetic analysis and electron tomography, we have identified the Actin-related protein (Arp) 2/3 complex as the major actin nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks the site of branchlet initiation in vivo. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation."}],"day":"04","doi":"10.1242/dev.171397","volume":146,"issue":"7","author":[{"full_name":"Stürner, Tomke","first_name":"Tomke","last_name":"Stürner"},{"full_name":"Tatarnikova, Anastasia","first_name":"Anastasia","last_name":"Tatarnikova"},{"full_name":"Müller, Jan","first_name":"Jan","last_name":"Müller","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D"},{"full_name":"Schaffran, Barbara","last_name":"Schaffran","first_name":"Barbara"},{"first_name":"Hermann","last_name":"Cuntz","full_name":"Cuntz, Hermann"},{"full_name":"Zhang, Yun","last_name":"Zhang","first_name":"Yun"},{"full_name":"Nemethova, Maria","first_name":"Maria","last_name":"Nemethova","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bogdan, Sven","first_name":"Sven","last_name":"Bogdan"},{"full_name":"Small, Vic","last_name":"Small","first_name":"Vic"},{"first_name":"Gaia","last_name":"Tavosanis","full_name":"Tavosanis, Gaia"}],"scopus_import":"1","pmid":1,"_id":"7404","intvolume":"       146","title":"Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo","date_created":"2020-01-29T16:27:10Z","department":[{"_id":"MiSi"}],"article_processing_charge":"No","publication_status":"published","quality_controlled":"1","article_type":"original","publisher":"The Company of Biologists","type":"journal_article","date_published":"2019-04-04T00:00:00Z","oa":1,"publication_identifier":{"issn":["0950-1991"],"eissn":["1477-9129"]},"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1242/dev.171397"}],"publication":"Development","article_number":"dev171397","month":"04","oa_version":"Published Version","language":[{"iso":"eng"}]},{"publication_status":"published","department":[{"_id":"DaZi"}],"article_processing_charge":"No","date_created":"2021-06-08T06:29:50Z","title":"Genome-wide analysis of DNA methylation patterns","intvolume":"       134","pmid":1,"_id":"9524","scopus_import":"1","author":[{"id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","first_name":"Daniel","last_name":"Zilberman","orcid":"0000-0002-0123-8649","full_name":"Zilberman, Daniel"},{"first_name":"Steven","last_name":"Henikoff","full_name":"Henikoff, Steven"}],"issue":"22","publisher":"The Company of Biologists","article_type":"review","page":"3959-3965","quality_controlled":"1","doi":"10.1242/dev.001131","day":"15","abstract":[{"text":"Cytosine methylation is the most common covalent modification of DNA in eukaryotes. DNA methylation has an important role in many aspects of biology, including development and disease. Methylation can be detected using bisulfite conversion, methylation-sensitive restriction enzymes, methyl-binding proteins and anti-methylcytosine antibodies. Combining these techniques with DNA microarrays and high-throughput sequencing has made the mapping of DNA methylation feasible on a genome-wide scale. Here we discuss recent developments and future directions for identifying and mapping methylation, in an effort to help colleagues to identify the approaches that best serve their research interests.","lang":"eng"}],"date_updated":"2021-12-14T08:57:58Z","year":"2007","citation":{"ista":"Zilberman D, Henikoff S. 2007. Genome-wide analysis of DNA methylation patterns. Development. 134(22), 3959–3965.","short":"D. Zilberman, S. Henikoff, Development 134 (2007) 3959–3965.","mla":"Zilberman, Daniel, and Steven Henikoff. “Genome-Wide Analysis of DNA Methylation Patterns.” <i>Development</i>, vol. 134, no. 22, The Company of Biologists, 2007, pp. 3959–65, doi:<a href=\"https://doi.org/10.1242/dev.001131\">10.1242/dev.001131</a>.","ieee":"D. Zilberman and S. Henikoff, “Genome-wide analysis of DNA methylation patterns,” <i>Development</i>, vol. 134, no. 22. The Company of Biologists, pp. 3959–3965, 2007.","chicago":"Zilberman, Daniel, and Steven Henikoff. “Genome-Wide Analysis of DNA Methylation Patterns.” <i>Development</i>. The Company of Biologists, 2007. <a href=\"https://doi.org/10.1242/dev.001131\">https://doi.org/10.1242/dev.001131</a>.","ama":"Zilberman D, Henikoff S. Genome-wide analysis of DNA methylation patterns. <i>Development</i>. 2007;134(22):3959-3965. doi:<a href=\"https://doi.org/10.1242/dev.001131\">10.1242/dev.001131</a>","apa":"Zilberman, D., &#38; Henikoff, S. (2007). Genome-wide analysis of DNA methylation patterns. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.001131\">https://doi.org/10.1242/dev.001131</a>"},"external_id":{"pmid":["17928417"]},"volume":134,"extern":"1","oa_version":"Published Version","month":"11","publication":"Development","language":[{"iso":"eng"}],"publication_identifier":{"issn":["0950-1991"],"eissn":["1477-9129"]},"oa":1,"date_published":"2007-11-15T00:00:00Z","type":"journal_article","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1242/dev.001131"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","status":"public"}]