[{"abstract":[{"text":"Developing tissues interpret dynamic changes in morphogen activity to generate cell type diversity. To quantitatively study bone morphogenetic protein (BMP) signaling dynamics in the mouse neural tube, we developed an embryonic stem cell differentiation system tailored for growing tissues. Differentiating cells form striking self-organized patterns of dorsal neural tube cell types driven by sequential phases of BMP signaling that are observed both in vitro and in vivo. Data-driven biophysical modeling showed that these dynamics result from coupling fast negative feedback with slow positive regulation of signaling by the specification of an endogenous BMP source. Thus, in contrast to relays that propagate morphogen signaling in space, we identify a BMP signaling relay that operates in time. This mechanism allows for a rapid initial concentration-sensitive response that is robustly terminated, thereby regulating balanced sequential cell type generation. Our study provides an experimental and theoretical framework to understand how signaling dynamics are exploited in developing tissues.","lang":"eng"}],"date_updated":"2026-06-15T22:31:04Z","author":[{"id":"4D9EC9B6-F248-11E8-B48F-1D18A9856A87","full_name":"Rus, Stefanie","last_name":"Rus","first_name":"Stefanie","orcid":"0000-0001-8703-1093"},{"first_name":"David","last_name":"Brückner","orcid":"0000-0001-7205-2975","id":"e1e86031-6537-11eb-953a-f7ab92be508d","full_name":"Brückner, David"},{"full_name":"Minchington, Thomas","id":"7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f","first_name":"Thomas","last_name":"Minchington"},{"full_name":"Greunz, Martina","id":"48A59534-F248-11E8-B48F-1D18A9856A87","last_name":"Greunz","first_name":"Martina"},{"first_name":"Jack","last_name":"Merrin","orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-6005-1561","first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kicheva, Anna","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4509-4998","last_name":"Kicheva","first_name":"Anna"}],"title":"Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling","external_id":{"isi":["001434279000001"],"pmid":["39603235"]},"date_created":"2025-01-09T11:25:47Z","project":[{"_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa","name":"Mechanisms of tissue size regulation in spinal cord development","grant_number":"101044579"},{"_id":"059DF620-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen control of growth and pattern in the spinal cord","grant_number":"F7802"},{"_id":"9B9B39FA-BA93-11EA-9121-9846C619BF3A","name":"The regulatory logic of pattern formation in the vertebrate dorsal neural tube","grant_number":"SC19-011"}],"corr_author":"1","date_published":"2025-02-24T00:00:00Z","OA_type":"hybrid","publication":"Developmental Cell","file_date_updated":"2025-04-16T10:54:07Z","pmid":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Elsevier","ddc":["570"],"citation":{"chicago":"Rus, Stefanie, David Brückner, Thomas Minchington, Martina Greunz, Jack Merrin, Edouard B Hannezo, and Anna Kicheva. “Self-Organized Pattern Formation in the Developing Mouse Neural Tube by a Temporal Relay of BMP Signaling.” <i>Developmental Cell</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.devcel.2024.10.024\">https://doi.org/10.1016/j.devcel.2024.10.024</a>.","apa":"Rus, S., Brückner, D., Minchington, T., Greunz, M., Merrin, J., Hannezo, E. B., &#38; Kicheva, A. (2025). Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2024.10.024\">https://doi.org/10.1016/j.devcel.2024.10.024</a>","ama":"Rus S, Brückner D, Minchington T, et al. Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling. <i>Developmental Cell</i>. 2025;60(4):567-580. doi:<a href=\"https://doi.org/10.1016/j.devcel.2024.10.024\">10.1016/j.devcel.2024.10.024</a>","ieee":"S. Rus <i>et al.</i>, “Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling,” <i>Developmental Cell</i>, vol. 60, no. 4. Elsevier, pp. 567–580, 2025.","mla":"Rus, Stefanie, et al. “Self-Organized Pattern Formation in the Developing Mouse Neural Tube by a Temporal Relay of BMP Signaling.” <i>Developmental Cell</i>, vol. 60, no. 4, Elsevier, 2025, pp. 567–80, doi:<a href=\"https://doi.org/10.1016/j.devcel.2024.10.024\">10.1016/j.devcel.2024.10.024</a>.","short":"S. Rus, D. Brückner, T. Minchington, M. Greunz, J. Merrin, E.B. Hannezo, A. Kicheva, Developmental Cell 60 (2025) 567–580.","ista":"Rus S, Brückner D, Minchington T, Greunz M, Merrin J, Hannezo EB, Kicheva A. 2025. Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling. Developmental Cell. 60(4), 567–580."},"quality_controlled":"1","article_processing_charge":"Yes (via OA deal)","oa_version":"Published Version","_id":"18807","day":"24","department":[{"_id":"AnKi"},{"_id":"EdHa"},{"_id":"NanoFab"}],"intvolume":"        60","article_type":"original","scopus_import":"1","isi":1,"license":"https://creativecommons.org/licenses/by/4.0/","month":"02","related_material":{"record":[{"id":"19763","status":"public","relation":"dissertation_contains"}]},"page":"567-580","has_accepted_license":"1","issue":"4","doi":"10.1016/j.devcel.2024.10.024","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"language":[{"iso":"eng"}],"file":[{"access_level":"open_access","success":1,"creator":"dernst","file_id":"19584","content_type":"application/pdf","checksum":"bb58db4a908a1f4aabe4004706154541","file_size":6994499,"file_name":"2025_DevelopmentalCell_Lehr.pdf","date_updated":"2025-04-16T10:54:07Z","date_created":"2025-04-16T10:54:07Z","relation":"main_file"}],"oa":1,"year":"2025","status":"public","publication_identifier":{"issn":["1534-5807"]},"OA_place":"publisher","volume":60,"type":"journal_article","acknowledgement":"We thank A. Miller and N. Papalopulu for reagents and J. Briscoe for comments on the manuscript. Work in the A.K. lab is supported by ISTA; the European Research Council under Horizon Europe, grant 101044579; and the Austrian Science Fund (FWF), grant https://doi.org/10.55776/F78. S.L. is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011. D.B.B. was supported by the NOMIS foundation as a NOMIS Fellow and by an EMBO Postdoctoral Fellowship (ALTF 343-2022)."},{"author":[{"full_name":"Ho, Richard D.J.G.","last_name":"Ho","first_name":"Richard D.J.G."},{"id":"3065DFC4-F248-11E8-B48F-1D18A9856A87","full_name":"Kishi, Kasumi","orcid":"0000-0001-6060-4795","first_name":"Kasumi","last_name":"Kishi"},{"full_name":"Majka, Maciej","last_name":"Majka","first_name":"Maciej"},{"last_name":"Kicheva","first_name":"Anna","orcid":"0000-0003-4509-4998","full_name":"Kicheva, Anna","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-7896-7762","last_name":"Zagórski","first_name":"Marcin P","full_name":"Zagórski, Marcin P","id":"343DA0DC-F248-11E8-B48F-1D18A9856A87"}],"title":"Dynamics of morphogen source formation in a growing tissue","external_id":{"pmid":["39401260"],"isi":["001331700300003"]},"date_created":"2024-10-27T23:01:45Z","project":[{"_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa","grant_number":"101044579","name":"Mechanisms of tissue size regulation in spinal cord development"},{"_id":"059DF620-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen control of growth and pattern in the spinal cord","grant_number":"F7802"}],"abstract":[{"text":"A tight regulation of morphogen production is key for morphogen gradient formation and thereby for reproducible and organised organ development. Although many genetic interactions involved in the establishment of morphogen production domains are known, the biophysical mechanisms of morphogen source formation are poorly understood. Here we addressed this by focusing on the morphogen Sonic hedgehog (Shh) in the vertebrate neural tube. Shh is produced by the adjacently located notochord and by the floor plate of the neural tube. Using a data-constrained computational screen, we identified different possible mechanisms by which floor plate formation can occur, only one of which is consistent with experimental data. In this mechanism, the floor plate is established rapidly in response to Shh from the notochord and the dynamics of regulatory interactions within the neural tube. In this process, uniform activators and Shh-dependent repressors are key for establishing the floor plate size. Subsequently, the floor plate becomes insensitive to Shh and increases in size due to tissue growth, leading to scaling of the floor plate with neural tube size. In turn, this results in scaling of the Shh amplitude with tissue growth. Thus, this mechanism ensures a separation of time scales in floor plate formation, so that the floor plate domain becomes growth-dependent after an initial rapid establishment phase. Our study raises the possibility that the time scale separation between specification and growth might be a common strategy for scaling the morphogen gradient amplitude in growing organs. The model that we developed provides a new opportunity for quantitative studies of morphogen source formation in growing tissues.","lang":"eng"}],"date_updated":"2026-04-07T12:31:58Z","file_date_updated":"2024-10-29T11:59:09Z","publication":"PLoS Computational Biology","pmid":1,"publication_status":"published","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","corr_author":"1","article_number":"e1012508","date_published":"2024-10-14T00:00:00Z","OA_type":"gold","ddc":["570"],"quality_controlled":"1","citation":{"ieee":"R. D. J. G. Ho, K. Kishi, M. Majka, A. Kicheva, and M. P. Zagórski, “Dynamics of morphogen source formation in a growing tissue,” <i>PLoS Computational Biology</i>, vol. 20. Public Library of Science, 2024.","mla":"Ho, Richard D. J. G., et al. “Dynamics of Morphogen Source Formation in a Growing Tissue.” <i>PLoS Computational Biology</i>, vol. 20, e1012508, Public Library of Science, 2024, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1012508\">10.1371/journal.pcbi.1012508</a>.","short":"R.D.J.G. Ho, K. Kishi, M. Majka, A. Kicheva, M.P. Zagórski, PLoS Computational Biology 20 (2024).","ista":"Ho RDJG, Kishi K, Majka M, Kicheva A, Zagórski MP. 2024. Dynamics of morphogen source formation in a growing tissue. PLoS Computational Biology. 20, e1012508.","chicago":"Ho, Richard D.J.G., Kasumi Kishi, Maciej Majka, Anna Kicheva, and Marcin P Zagórski. “Dynamics of Morphogen Source Formation in a Growing Tissue.” <i>PLoS Computational Biology</i>. Public Library of Science, 2024. <a href=\"https://doi.org/10.1371/journal.pcbi.1012508\">https://doi.org/10.1371/journal.pcbi.1012508</a>.","apa":"Ho, R. D. J. G., Kishi, K., Majka, M., Kicheva, A., &#38; Zagórski, M. P. (2024). Dynamics of morphogen source formation in a growing tissue. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1012508\">https://doi.org/10.1371/journal.pcbi.1012508</a>","ama":"Ho RDJG, Kishi K, Majka M, Kicheva A, Zagórski MP. Dynamics of morphogen source formation in a growing tissue. <i>PLoS Computational Biology</i>. 2024;20. doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1012508\">10.1371/journal.pcbi.1012508</a>"},"publisher":"Public Library of Science","department":[{"_id":"AnKi"}],"intvolume":"        20","article_type":"original","scopus_import":"1","article_processing_charge":"No","oa_version":"Published Version","_id":"18481","day":"14","month":"10","DOAJ_listed":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"file_name":"2024_PloSComBio_Ho.pdf","date_updated":"2024-10-29T11:59:09Z","checksum":"42fa714459943cb3961b40fab8fd82c8","file_size":3732443,"content_type":"application/pdf","date_created":"2024-10-29T11:59:09Z","relation":"main_file","access_level":"open_access","creator":"dernst","success":1,"file_id":"18487"}],"language":[{"iso":"eng"}],"oa":1,"year":"2024","has_accepted_license":"1","related_material":{"record":[{"relation":"dissertation_contains","id":"20393","status":"public"}]},"doi":"10.1371/journal.pcbi.1012508","OA_place":"publisher","volume":20,"status":"public","publication_identifier":{"issn":["1553-734X"],"eissn":["1553-7358"]},"acknowledgement":"We thank Martina Greunz-Schindler for technical support, and Thomas Minchington and James Briscoe for comments on the manuscript.\r\nRDJGH, MM and MZ were supported by a grant from the Priority Research Area DigiWorld\r\nunder the Strategic Programme Excellence Initiative at Jagiellonian University. The research\r\nwas supported by the Polish National Agency for Academic Exchange, PN/PPO/2018/1/00011/U/00001 which paid the salary of MM and MZ up to Feb 2023. The research received support from National Science Center, Poland, 2021/42/E/NZ2/00188 which paid salary of MZ. Work in the AK labis supported by ISTA to KK and AK, the European\r\nResearch Council under Horizon Europe: grant 101044579 to AK, and Austrian Science Fund\r\n(FWF): Grant DOI 10.55776/F78 to AK. The salaries of AK and KK were paid by ISTA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","APC_amount":"3197,23 EUR","type":"journal_article"},{"OA_place":"publisher","volume":15,"status":"public","publication_identifier":{"eissn":["2041-1723"]},"acknowledgement":"MZ is supported by National Science Center, Poland, 2021/42/E/NZ2/00188, the Polish National Agency for Academic Exchange, and by a grant from the Priority Research Area DigiWorld under the Strategic Programme Excellence Initiative at Jagiellonian University. Work in JB’s lab is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council and Wellcome Trust (all under CC001051). Work in the AK lab is supported by ISTA, the European Research Council under Horizon Europe: grant 101044579, and Austrian Science Fund (FWF): F78 (Neural Stem Cell Modulation).","type":"journal_article","month":"02","DOAJ_listed":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"file_size":4723831,"content_type":"application/pdf","checksum":"acf75f2b6fa84a64d1f590dd4a53cbf7","file_name":"2024_NatureComm_Zagorski.pdf","date_updated":"2025-01-27T13:04:03Z","relation":"main_file","date_created":"2025-01-27T13:04:03Z","success":1,"creator":"dernst","access_level":"open_access","file_id":"18903"}],"language":[{"iso":"eng"}],"oa":1,"year":"2024","has_accepted_license":"1","doi":"10.1038/s41467-024-45148-8","ddc":["570"],"quality_controlled":"1","citation":{"chicago":"Zagorski, Marcin, Nathalie Brandenberg, Matthias Lutolf, Gašper Tkačik, Mark Tobias Bollenbach, James Briscoe, and Anna Kicheva. “Assessing the Precision of Morphogen Gradients in Neural Tube Development.” <i>Nature Communications</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41467-024-45148-8\">https://doi.org/10.1038/s41467-024-45148-8</a>.","ama":"Zagorski M, Brandenberg N, Lutolf M, et al. Assessing the precision of morphogen gradients in neural tube development. <i>Nature Communications</i>. 2024;15. doi:<a href=\"https://doi.org/10.1038/s41467-024-45148-8\">10.1038/s41467-024-45148-8</a>","apa":"Zagorski, M., Brandenberg, N., Lutolf, M., Tkačik, G., Bollenbach, M. T., Briscoe, J., &#38; Kicheva, A. (2024). Assessing the precision of morphogen gradients in neural tube development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-024-45148-8\">https://doi.org/10.1038/s41467-024-45148-8</a>","short":"M. Zagorski, N. Brandenberg, M. Lutolf, G. Tkačik, M.T. Bollenbach, J. Briscoe, A. Kicheva, Nature Communications 15 (2024).","mla":"Zagorski, Marcin, et al. “Assessing the Precision of Morphogen Gradients in Neural Tube Development.” <i>Nature Communications</i>, vol. 15, 929, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1038/s41467-024-45148-8\">10.1038/s41467-024-45148-8</a>.","ieee":"M. Zagorski <i>et al.</i>, “Assessing the precision of morphogen gradients in neural tube development,” <i>Nature Communications</i>, vol. 15. Springer Nature, 2024.","ista":"Zagorski M, Brandenberg N, Lutolf M, Tkačik G, Bollenbach MT, Briscoe J, Kicheva A. 2024. Assessing the precision of morphogen gradients in neural tube development. Nature Communications. 15, 929."},"publisher":"Springer Nature","department":[{"_id":"GaTk"},{"_id":"AnKi"}],"intvolume":"        15","article_type":"letter_note","scopus_import":"1","oa_version":"Published Version","article_processing_charge":"Yes","_id":"18902","day":"01","title":"Assessing the precision of morphogen gradients in neural tube development","author":[{"full_name":"Zagorski, Marcin","first_name":"Marcin","last_name":"Zagorski"},{"full_name":"Brandenberg, Nathalie","first_name":"Nathalie","last_name":"Brandenberg"},{"last_name":"Lutolf","first_name":"Matthias","full_name":"Lutolf, Matthias"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik"},{"last_name":"Bollenbach","first_name":"Mark Tobias","orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Briscoe, James","first_name":"James","last_name":"Briscoe"},{"full_name":"Kicheva, Anna","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4509-4998","first_name":"Anna","last_name":"Kicheva"}],"external_id":{"isi":["001156218500022"],"pmid":["38302459"]},"date_created":"2025-01-27T13:01:01Z","project":[{"_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa","name":"Mechanisms of tissue size regulation in spinal cord development","grant_number":"101044579"},{"grant_number":"F7802","name":"Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen control of growth and pattern in the spinal cord","_id":"059DF620-7A3F-11EA-A408-12923DDC885E"}],"date_updated":"2025-12-30T10:57:08Z","file_date_updated":"2025-01-27T13:04:03Z","publication":"Nature Communications","pmid":1,"publication_status":"published","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","corr_author":"1","article_number":"929","date_published":"2024-02-01T00:00:00Z","OA_type":"gold"},{"file_date_updated":"2025-01-13T10:59:12Z","publication":"Developmental Cell","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","publication_status":"published","pmid":1,"OA_type":"hybrid","date_published":"2024-08-01T00:00:00Z","date_created":"2024-06-16T22:01:07Z","external_id":{"isi":["001289684800001"],"pmid":["38776925"]},"title":"Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition","author":[{"last_name":"Krammer","first_name":"Teresa","full_name":"Krammer, Teresa"},{"full_name":"Stuart, Hannah T.","first_name":"Hannah T.","last_name":"Stuart"},{"last_name":"Gromberg","first_name":"Elena","full_name":"Gromberg, Elena"},{"full_name":"Ishihara, Keisuke","first_name":"Keisuke","last_name":"Ishihara"},{"full_name":"Cislo, Dillon","first_name":"Dillon","last_name":"Cislo"},{"first_name":"Manuela","last_name":"Melchionda","full_name":"Melchionda, Manuela"},{"full_name":"Becerril Perez, Fernando","first_name":"Fernando","last_name":"Becerril Perez"},{"full_name":"Wang, Jingkui","first_name":"Jingkui","last_name":"Wang"},{"last_name":"Costantini","first_name":"Elena","full_name":"Costantini, Elena"},{"id":"4D9EC9B6-F248-11E8-B48F-1D18A9856A87","full_name":"Rus, Stefanie","first_name":"Stefanie","last_name":"Rus","orcid":"0000-0001-8703-1093"},{"last_name":"Arbanas","first_name":"Laura","full_name":"Arbanas, Laura"},{"first_name":"Alexandra","last_name":"Hörmann","full_name":"Hörmann, Alexandra"},{"full_name":"Neumüller, Ralph A.","last_name":"Neumüller","first_name":"Ralph A."},{"full_name":"Elvassore, Nicola","first_name":"Nicola","last_name":"Elvassore"},{"first_name":"Eric","last_name":"Siggia","full_name":"Siggia, Eric"},{"full_name":"Briscoe, James","first_name":"James","last_name":"Briscoe"},{"id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","full_name":"Kicheva, Anna","orcid":"0000-0003-4509-4998","first_name":"Anna","last_name":"Kicheva"},{"full_name":"Tanaka, Elly M.","last_name":"Tanaka","first_name":"Elly M."}],"project":[{"_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa","grant_number":"101044579","name":"Mechanisms of tissue size regulation in spinal cord development"},{"grant_number":"SC19-011","name":"The regulatory logic of pattern formation in the vertebrate dorsal neural tube","_id":"9B9B39FA-BA93-11EA-9121-9846C619BF3A"}],"abstract":[{"text":"During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially spatially scattered before resolving into multiple clusters, which underwent competition and sorting, resulting in a stable “winning” floorplate. We identified that BMP signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4, suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the floorplate can form autonomously without the notochord. Identifying the pathways governing organizer self-organization is critical for harnessing the developmental plasticity of stem cells in tissue engineering.","lang":"eng"}],"date_updated":"2026-06-15T22:31:04Z","intvolume":"        59","department":[{"_id":"AnKi"}],"article_type":"original","scopus_import":"1","_id":"17148","oa_version":"Published Version","article_processing_charge":"Yes (in subscription journal)","day":"01","ddc":["570"],"citation":{"ieee":"T. Krammer <i>et al.</i>, “Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition,” <i>Developmental Cell</i>, vol. 59, no. 15. Elsevier, p. 1940–1953.e10, 2024.","short":"T. Krammer, H.T. Stuart, E. Gromberg, K. Ishihara, D. Cislo, M. Melchionda, F. Becerril Perez, J. Wang, E. Costantini, S. Rus, L. Arbanas, A. Hörmann, R.A. Neumüller, N. Elvassore, E. Siggia, J. Briscoe, A. Kicheva, E.M. Tanaka, Developmental Cell 59 (2024) 1940–1953.e10.","mla":"Krammer, Teresa, et al. “Mouse Neural Tube Organoids Self-Organize Floorplate through BMP-Mediated Cluster Competition.” <i>Developmental Cell</i>, vol. 59, no. 15, Elsevier, 2024, p. 1940–1953.e10, doi:<a href=\"https://doi.org/10.1016/j.devcel.2024.04.021\">10.1016/j.devcel.2024.04.021</a>.","ista":"Krammer T, Stuart HT, Gromberg E, Ishihara K, Cislo D, Melchionda M, Becerril Perez F, Wang J, Costantini E, Rus S, Arbanas L, Hörmann A, Neumüller RA, Elvassore N, Siggia E, Briscoe J, Kicheva A, Tanaka EM. 2024. Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. Developmental Cell. 59(15), 1940–1953.e10.","chicago":"Krammer, Teresa, Hannah T. Stuart, Elena Gromberg, Keisuke Ishihara, Dillon Cislo, Manuela Melchionda, Fernando Becerril Perez, et al. “Mouse Neural Tube Organoids Self-Organize Floorplate through BMP-Mediated Cluster Competition.” <i>Developmental Cell</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.devcel.2024.04.021\">https://doi.org/10.1016/j.devcel.2024.04.021</a>.","ama":"Krammer T, Stuart HT, Gromberg E, et al. Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. <i>Developmental Cell</i>. 2024;59(15):1940-1953.e10. doi:<a href=\"https://doi.org/10.1016/j.devcel.2024.04.021\">10.1016/j.devcel.2024.04.021</a>","apa":"Krammer, T., Stuart, H. T., Gromberg, E., Ishihara, K., Cislo, D., Melchionda, M., … Tanaka, E. M. (2024). Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2024.04.021\">https://doi.org/10.1016/j.devcel.2024.04.021</a>"},"quality_controlled":"1","publisher":"Elsevier","language":[{"iso":"eng"}],"file":[{"date_created":"2025-01-13T10:59:12Z","relation":"main_file","content_type":"application/pdf","file_size":6249076,"checksum":"fefdea9c02862b4bb74de49b65ce638a","file_name":"2024_DevelopmentalCell_Krammer.pdf","date_updated":"2025-01-13T10:59:12Z","file_id":"18841","access_level":"open_access","success":1,"creator":"dernst"}],"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"},"year":"2024","oa":1,"doi":"10.1016/j.devcel.2024.04.021","issue":"15","page":"1940-1953.e10","has_accepted_license":"1","related_material":{"record":[{"status":"public","id":"19763","relation":"dissertation_contains"}]},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","month":"08","isi":1,"acknowledgement":"We thank P. Pasierbek, A.C. Moreno, T. Lendl, and K. Aumayr for microscopy support; G. Schmauss for FACS support; M. Novatchkova for assistance with Bioinformatic analyses; J. Ahel, A. Polikarpova, S. Horer, E. Cesare, and E. Norouzi for technical assistance; A. Meinhardt for supervision; DRESDEN-concept Genome Center, A. Vogt, A. Sommer, and the Vienna BioCenter NGS facility for RNA sequencing. We are grateful to M. Placzek and E. Martí for discussions about the floorplate; to S. Shvartsman for valuable input; to A. Aszodi, W. Masselink, and S. Raiders for advice on statistical analyses; to J. Cornwall Scoones, G. Martello, and Tanaka lab members for critical reading of the manuscript; E. Bassat and E. Chatzidaki for contributing schematics; and to K. Lust for support. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement ERC AdG 742046) to E.M.T. This research was funded in whole or in part by the Austrian Science Fund (FWF) (10.55776/F7803-B) (Stem Cell Modulation) to E.M.T. and A.K., Sir Henry Wellcome postdoctoral fellowship to H.T.S., ELBE fellowship to K.I., and National Science Foundation (US) Phy 2013131 to E.S. The A.K. lab is also supported by ISTA and the European Research Council under Horizon Europe grant 101044579, and S.L. is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011. This work was supported in part by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC001051), the UK Medical Research Council (CC001051), and the Wellcome Trust (CC001051). For the purpose of open access, the authors have applied a CC BY public copyright license to any author accepted manuscript (AAM) version arising from this submission.","type":"journal_article","volume":59,"OA_place":"publisher","status":"public","publication_identifier":{"issn":["1534-5807"],"eissn":["1878-1551"]}},{"quality_controlled":"1","citation":{"apa":"Rus, S., Merrin, J., Kulig, M. A., Minchington, T., &#38; Kicheva, A. (2024). Protocol for fabricating elastomeric stencils for patterned stem cell differentiation. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2024.103187\">https://doi.org/10.1016/j.xpro.2024.103187</a>","ama":"Rus S, Merrin J, Kulig MA, Minchington T, Kicheva A. Protocol for fabricating elastomeric stencils for patterned stem cell differentiation. <i>STAR Protocols</i>. 2024;5(4). doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103187\">10.1016/j.xpro.2024.103187</a>","chicago":"Rus, Stefanie, Jack Merrin, Monika Aleksandra Kulig, Thomas Minchington, and Anna Kicheva. “Protocol for Fabricating Elastomeric Stencils for Patterned Stem Cell Differentiation.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2024.103187\">https://doi.org/10.1016/j.xpro.2024.103187</a>.","ista":"Rus S, Merrin J, Kulig MA, Minchington T, Kicheva A. 2024. Protocol for fabricating elastomeric stencils for patterned stem cell differentiation. STAR Protocols. 5(4), 103187.","ieee":"S. Rus, J. Merrin, M. A. Kulig, T. Minchington, and A. Kicheva, “Protocol for fabricating elastomeric stencils for patterned stem cell differentiation,” <i>STAR Protocols</i>, vol. 5, no. 4. Elsevier, 2024.","short":"S. Rus, J. Merrin, M.A. Kulig, T. Minchington, A. Kicheva, STAR Protocols 5 (2024).","mla":"Rus, Stefanie, et al. “Protocol for Fabricating Elastomeric Stencils for Patterned Stem Cell Differentiation.” <i>STAR Protocols</i>, vol. 5, no. 4, 103187, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103187\">10.1016/j.xpro.2024.103187</a>."},"ddc":["570"],"acknowledged_ssus":[{"_id":"NanoFab"}],"publisher":"Elsevier","scopus_import":"1","article_type":"original","intvolume":"         5","department":[{"_id":"AnKi"},{"_id":"NanoFab"}],"day":"20","_id":"18601","article_processing_charge":"Yes","oa_version":"Published Version","project":[{"grant_number":"101044579","name":"Mechanisms of tissue size regulation in spinal cord development","_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa"},{"name":"The regulatory logic of pattern formation in the vertebrate dorsal neural tube","grant_number":"SC19-011","_id":"9B9B39FA-BA93-11EA-9121-9846C619BF3A"}],"date_created":"2024-12-01T23:01:53Z","external_id":{"pmid":["39602310"]},"author":[{"full_name":"Rus, Stefanie","id":"4D9EC9B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8703-1093","last_name":"Rus","first_name":"Stefanie"},{"orcid":"0000-0001-5145-4609","first_name":"Jack","last_name":"Merrin","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kulig, Monika Aleksandra","id":"3331f5ae-e896-11ec-af79-eeb79769bcb7","last_name":"Kulig","first_name":"Monika Aleksandra"},{"id":"7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f","full_name":"Minchington, Thomas","last_name":"Minchington","first_name":"Thomas"},{"first_name":"Anna","last_name":"Kicheva","orcid":"0000-0003-4509-4998","full_name":"Kicheva, Anna","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87"}],"title":"Protocol for fabricating elastomeric stencils for patterned stem cell differentiation","date_updated":"2026-06-15T22:31:04Z","abstract":[{"text":"Geometrically controlled stem cell differentiation promotes reproducible pattern formation. Here, we present a protocol to fabricate elastomeric stencils for patterned stem cell differentiation. We describe procedures for using photolithography to produce molds, followed by molding polydimethylsiloxane (PDMS) to obtain stencils with through holes. We then provide instructions for culturing cells on stencils and, finally, removing stencils to allow colony growth and cell migration. This approach yields reproducible two-dimensional organoids tailored for quantitative studies of growth and pattern formation.\r\nFor complete details on the use and execution of this protocol, please refer to Lehr et al.1","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"publication_status":"published","publication":"STAR Protocols","file_date_updated":"2024-12-03T10:53:23Z","OA_type":"gold","date_published":"2024-12-20T00:00:00Z","article_number":"103187","corr_author":"1","volume":5,"OA_place":"publisher","publication_identifier":{"eissn":["2666-1667"]},"status":"public","APC_amount":"804 EUR","acknowledgement":"We thank the nanofabrication facility at ISTA for technical assistance. Work in the A.K. lab is supported by ISTA, the European Research Council under Horizon Europe (grant 101044579), and the Austrian Science Fund (FWF) (grant https://doi.org/10.55776/F78). S.L. is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011.","type":"journal_article","month":"12","DOAJ_listed":"1","year":"2024","oa":1,"file":[{"file_name":"2024_STARProtoc_Lehr.pdf","date_updated":"2024-12-03T10:53:23Z","content_type":"application/pdf","checksum":"0c61a6f9978608a103865905e06f4581","file_size":4989169,"relation":"main_file","date_created":"2024-12-03T10:53:23Z","creator":"dernst","success":1,"access_level":"open_access","file_id":"18610"}],"language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"issue":"4","doi":"10.1016/j.xpro.2024.103187","related_material":{"record":[{"id":"19763","status":"public","relation":"dissertation_contains"}]},"has_accepted_license":"1"},{"date_updated":"2025-12-30T10:57:08Z","abstract":[{"text":"Intercellular signaling molecules, known as morphogens, act at a long range in developing tissues to provide spatial information and control properties such as cell fate and tissue growth. The production, transport, and removal of morphogens shape their concentration profiles in time and space. Downstream signaling cascades and gene regulatory networks within cells then convert the spatiotemporal morphogen profiles into distinct cellular responses. Current challenges are to understand the diverse molecular and cellular mechanisms underlying morphogen gradient formation, as well as the logic of downstream regulatory circuits involved in morphogen interpretation. This knowledge, combining experimental and theoretical results, is essential to understand emerging properties of morphogen-controlled systems, such as robustness and scaling.","lang":"eng"}],"project":[{"call_identifier":"H2020","grant_number":"680037","name":"Coordination of Patterning And Growth In the Spinal Cord","_id":"B6FC0238-B512-11E9-945C-1524E6697425"},{"name":"Mechanisms of tissue size regulation in spinal cord development","grant_number":"101044579","_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen control of growth and pattern in the spinal cord","grant_number":"F7802","_id":"059DF620-7A3F-11EA-A408-12923DDC885E"}],"title":"Control of tissue development by morphogens","author":[{"id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","full_name":"Kicheva, Anna","first_name":"Anna","last_name":"Kicheva","orcid":"0000-0003-4509-4998"},{"first_name":"James","last_name":"Briscoe","full_name":"Briscoe, James"}],"external_id":{"pmid":["37418774"],"isi":["001082823000006"]},"date_created":"2023-11-05T23:00:53Z","date_published":"2023-10-16T00:00:00Z","corr_author":"1","pmid":1,"publication_status":"published","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","file_date_updated":"2023-11-06T09:47:50Z","publication":"Annual Review of Cell and Developmental Biology","publisher":"Annual Reviews","citation":{"ista":"Kicheva A, Briscoe J. 2023. Control of tissue development by morphogens. Annual Review of Cell and Developmental Biology. 39, 91–121.","ieee":"A. Kicheva and J. Briscoe, “Control of tissue development by morphogens,” <i>Annual Review of Cell and Developmental Biology</i>, vol. 39. Annual Reviews, pp. 91–121, 2023.","short":"A. Kicheva, J. Briscoe, Annual Review of Cell and Developmental Biology 39 (2023) 91–121.","mla":"Kicheva, Anna, and James Briscoe. “Control of Tissue Development by Morphogens.” <i>Annual Review of Cell and Developmental Biology</i>, vol. 39, Annual Reviews, 2023, pp. 91–121, doi:<a href=\"https://doi.org/10.1146/annurev-cellbio-020823-011522\">10.1146/annurev-cellbio-020823-011522</a>.","apa":"Kicheva, A., &#38; Briscoe, J. (2023). Control of tissue development by morphogens. <i>Annual Review of Cell and Developmental Biology</i>. Annual Reviews. <a href=\"https://doi.org/10.1146/annurev-cellbio-020823-011522\">https://doi.org/10.1146/annurev-cellbio-020823-011522</a>","ama":"Kicheva A, Briscoe J. Control of tissue development by morphogens. <i>Annual Review of Cell and Developmental Biology</i>. 2023;39:91-121. doi:<a href=\"https://doi.org/10.1146/annurev-cellbio-020823-011522\">10.1146/annurev-cellbio-020823-011522</a>","chicago":"Kicheva, Anna, and James Briscoe. “Control of Tissue Development by Morphogens.” <i>Annual Review of Cell and Developmental Biology</i>. Annual Reviews, 2023. <a href=\"https://doi.org/10.1146/annurev-cellbio-020823-011522\">https://doi.org/10.1146/annurev-cellbio-020823-011522</a>."},"quality_controlled":"1","ddc":["570"],"day":"16","article_processing_charge":"Yes (in subscription journal)","oa_version":"Published Version","_id":"14484","article_type":"review","scopus_import":"1","department":[{"_id":"AnKi"}],"intvolume":"        39","isi":1,"month":"10","has_accepted_license":"1","page":"91-121","doi":"10.1146/annurev-cellbio-020823-011522","oa":1,"year":"2023","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"language":[{"iso":"eng"}],"file":[{"relation":"main_file","date_created":"2023-11-06T09:47:50Z","content_type":"application/pdf","file_size":434819,"checksum":"461726014cf5907010afbd418d3c13ec","file_name":"2023_AnnualReviews_Kicheva.pdf","date_updated":"2023-11-06T09:47:50Z","file_id":"14491","success":1,"creator":"dernst","access_level":"open_access"}],"publication_identifier":{"issn":["1081-0706"],"eissn":["1530-8995"]},"ec_funded":1,"status":"public","volume":39,"type":"journal_article","acknowledgement":"We are grateful to Zena Hadjivasiliou for comments on this article. A.K. is supported by grants from the European Research Council under the European Union (EU) Horizon 2020 research and innovation program (680037) and Horizon Europe (101044579), and the Austrian Science Fund (F78) (Stem Cell Modulation). J.B. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC001051), the UK Medical Research Council (CC001051), and the Wellcome Trust (CC001051), and by a grant from the European Research Council under the EU Horizon 2020 research and innovation program (742138)."},{"month":"09","oa":1,"year":"2023","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"},"language":[{"iso":"eng"}],"file":[{"success":1,"creator":"dernst","access_level":"open_access","file_id":"14896","file_size":598842,"checksum":"8a75c4e29fd9b62e3c50663c2265b173","content_type":"application/pdf","date_updated":"2024-01-29T11:06:45Z","file_name":"2023_CurrOpSystBioloy_Minchington.pdf","relation":"main_file","date_created":"2024-01-29T11:06:45Z"}],"has_accepted_license":"1","related_material":{"record":[{"status":"public","id":"19763","relation":"dissertation_contains"}]},"doi":"10.1016/j.coisb.2023.100459","volume":35,"publication_identifier":{"eissn":["2452-3100"]},"status":"public","acknowledgement":"We thank J. Briscoe for comments on the manuscript. Work in the AK lab is supported by ISTA, the European Research Council under Horizon Europe: grant 101044579, and Austrian Science Fund (FWF): F78 (Stem Cell Modulation). SR is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011.","type":"journal_article","project":[{"_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa","name":"Mechanisms of tissue size regulation in spinal cord development","grant_number":"101044579"},{"_id":"059DF620-7A3F-11EA-A408-12923DDC885E","grant_number":"F7802","name":"Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen control of growth and pattern in the spinal cord"},{"name":"The regulatory logic of pattern formation in the vertebrate dorsal neural tube","grant_number":"SC19-011","_id":"9B9B39FA-BA93-11EA-9121-9846C619BF3A"}],"title":"Control of tissue dimensions in the developing neural tube and somites","author":[{"last_name":"Minchington","first_name":"Thomas","id":"7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f","full_name":"Minchington, Thomas"},{"full_name":"Rus, Stefanie","id":"4D9EC9B6-F248-11E8-B48F-1D18A9856A87","first_name":"Stefanie","last_name":"Rus","orcid":"0000-0001-8703-1093"},{"id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","full_name":"Kicheva, Anna","orcid":"0000-0003-4509-4998","last_name":"Kicheva","first_name":"Anna"}],"date_created":"2023-06-18T22:00:46Z","date_updated":"2026-06-15T22:31:05Z","abstract":[{"lang":"eng","text":"Despite its fundamental importance for development, the question of how organs achieve their correct size and shape is poorly understood. This complex process requires coordination between the generation of cell mass and the morphogenetic mechanisms that sculpt tissues. These processes are regulated by morphogen signalling pathways and mechanical forces. Yet, in many systems, it is unclear how biochemical and mechanical signalling are quantitatively interpreted to determine the behaviours of individual cells and how they contribute to growth and morphogenesis at the tissue scale. In this review, we discuss the development of the vertebrate neural tube and somites as an example of the state of knowledge, as well as the challenges in understanding the mechanisms of tissue size control in vertebrate organogenesis. We highlight how the recent advances in stem cell differentiation and organoid approaches can be harnessed to provide new insights into this question."}],"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2024-01-29T11:06:45Z","publication":"Current Opinion in Systems Biology","date_published":"2023-09-01T00:00:00Z","corr_author":"1","article_number":"100459","quality_controlled":"1","citation":{"chicago":"Minchington, Thomas, Stefanie Rus, and Anna Kicheva. “Control of Tissue Dimensions in the Developing Neural Tube and Somites.” <i>Current Opinion in Systems Biology</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.coisb.2023.100459\">https://doi.org/10.1016/j.coisb.2023.100459</a>.","apa":"Minchington, T., Rus, S., &#38; Kicheva, A. (2023). Control of tissue dimensions in the developing neural tube and somites. <i>Current Opinion in Systems Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.coisb.2023.100459\">https://doi.org/10.1016/j.coisb.2023.100459</a>","ama":"Minchington T, Rus S, Kicheva A. Control of tissue dimensions in the developing neural tube and somites. <i>Current Opinion in Systems Biology</i>. 2023;35. doi:<a href=\"https://doi.org/10.1016/j.coisb.2023.100459\">10.1016/j.coisb.2023.100459</a>","ieee":"T. Minchington, S. Rus, and A. Kicheva, “Control of tissue dimensions in the developing neural tube and somites,” <i>Current Opinion in Systems Biology</i>, vol. 35. Elsevier, 2023.","mla":"Minchington, Thomas, et al. “Control of Tissue Dimensions in the Developing Neural Tube and Somites.” <i>Current Opinion in Systems Biology</i>, vol. 35, 100459, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.coisb.2023.100459\">10.1016/j.coisb.2023.100459</a>.","short":"T. Minchington, S. Rus, A. Kicheva, Current Opinion in Systems Biology 35 (2023).","ista":"Minchington T, Rus S, Kicheva A. 2023. Control of tissue dimensions in the developing neural tube and somites. Current Opinion in Systems Biology. 35, 100459."},"ddc":["570"],"publisher":"Elsevier","article_type":"original","scopus_import":"1","department":[{"_id":"AnKi"}],"intvolume":"        35","day":"01","article_processing_charge":"Yes (via OA deal)","oa_version":"Published Version","_id":"13136"},{"pmid":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2023-10-04T11:13:28Z","publication":"Nature Physics","date_published":"2023-07-01T00:00:00Z","corr_author":"1","project":[{"call_identifier":"H2020","grant_number":"680037","name":"Coordination of Patterning And Growth In the Spinal Cord","_id":"B6FC0238-B512-11E9-945C-1524E6697425"},{"grant_number":"101044579","name":"Mechanisms of tissue size regulation in spinal cord development","_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa"},{"_id":"059DF620-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen control of growth and pattern in the spinal cord","grant_number":"F7802"},{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"author":[{"last_name":"Bocanegra","first_name":"Laura","id":"4896F754-F248-11E8-B48F-1D18A9856A87","full_name":"Bocanegra, Laura"},{"first_name":"Amrita","last_name":"Singh","full_name":"Singh, Amrita","id":"76250f9f-3a21-11eb-9a80-a6180a0d7958"},{"full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","last_name":"Hannezo","orcid":"0000-0001-6005-1561"},{"id":"343DA0DC-F248-11E8-B48F-1D18A9856A87","full_name":"Zagórski, Marcin P","orcid":"0000-0001-7896-7762","first_name":"Marcin P","last_name":"Zagórski"},{"id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","full_name":"Kicheva, Anna","orcid":"0000-0003-4509-4998","last_name":"Kicheva","first_name":"Anna"}],"title":"Cell cycle dynamics control fluidity of the developing mouse neuroepithelium","external_id":{"pmid":["37456593"],"isi":["000964029300003"]},"date_created":"2023-04-16T22:01:09Z","date_updated":"2026-06-15T22:31:07Z","abstract":[{"lang":"eng","text":"As developing tissues grow in size and undergo morphogenetic changes, their material properties may be altered. Such changes result from tension dynamics at cell contacts or cellular jamming. Yet, in many cases, the cellular mechanisms controlling the physical state of growing tissues are unclear. We found that at early developmental stages, the epithelium in the developing mouse spinal cord maintains both high junctional tension and high fluidity. This is achieved via a mechanism in which interkinetic nuclear movements generate cell area dynamics that drive extensive cell rearrangements. Over time, the cell proliferation rate declines, effectively solidifying the tissue. Thus, unlike well-studied jamming transitions, the solidification uncovered here resembles a glass transition that depends on the dynamical stresses generated by proliferation and differentiation. Our finding that the fluidity of developing epithelia is linked to interkinetic nuclear movements and the dynamics of growth is likely to be relevant to multiple developing tissues."}],"article_type":"original","scopus_import":"1","department":[{"_id":"EdHa"},{"_id":"AnKi"}],"intvolume":"        19","day":"01","oa_version":"Published Version","article_processing_charge":"No","_id":"12837","citation":{"mla":"Bocanegra, Laura, et al. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.” <i>Nature Physics</i>, vol. 19, Springer Nature, 2023, pp. 1050–58, doi:<a href=\"https://doi.org/10.1038/s41567-023-01977-w\">10.1038/s41567-023-01977-w</a>.","short":"L. Bocanegra, A. Singh, E.B. Hannezo, M.P. Zagórski, A. Kicheva, Nature Physics 19 (2023) 1050–1058.","ieee":"L. Bocanegra, A. Singh, E. B. Hannezo, M. P. Zagórski, and A. Kicheva, “Cell cycle dynamics control fluidity of the developing mouse neuroepithelium,” <i>Nature Physics</i>, vol. 19. Springer Nature, pp. 1050–1058, 2023.","ista":"Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. 2023. Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics. 19, 1050–1058.","chicago":"Bocanegra, Laura, Amrita Singh, Edouard B Hannezo, Marcin P Zagórski, and Anna Kicheva. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.” <i>Nature Physics</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41567-023-01977-w\">https://doi.org/10.1038/s41567-023-01977-w</a>.","apa":"Bocanegra, L., Singh, A., Hannezo, E. B., Zagórski, M. P., &#38; Kicheva, A. (2023). Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-023-01977-w\">https://doi.org/10.1038/s41567-023-01977-w</a>","ama":"Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. <i>Nature Physics</i>. 2023;19:1050-1058. doi:<a href=\"https://doi.org/10.1038/s41567-023-01977-w\">10.1038/s41567-023-01977-w</a>"},"quality_controlled":"1","ddc":["570"],"publisher":"Springer Nature","oa":1,"year":"2023","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"date_updated":"2023-10-04T11:13:28Z","file_name":"2023_NaturePhysics_Boncanegra.pdf","checksum":"858225a4205b74406e5045006cdd853f","file_size":5532285,"content_type":"application/pdf","date_created":"2023-10-04T11:13:28Z","relation":"main_file","access_level":"open_access","creator":"dernst","success":1,"file_id":"14392"}],"language":[{"iso":"eng"}],"has_accepted_license":"1","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"13081"}]},"page":"1050-1058","doi":"10.1038/s41567-023-01977-w","month":"07","isi":1,"acknowledgement":"We thank S. Hippenmeyer for the reagents and C. P. Heisenberg, J. Briscoe and K. Page for comments on the manuscript. This work was supported by IST Austria; the European Research Council under Horizon 2020 research and innovation programme grant no. 680037 and Horizon Europe grant 101044579 (A.K.); Austrian Science Fund (FWF): F78 (Stem Cell Modulation) (A.K.); ISTFELLOW postdoctoral program (A.S.); Narodowe Centrum Nauki, Poland SONATA, 2017/26/D/NZ2/00454 (M.Z.); and the Polish National Agency for Academic Exchange (M.Z.).","type":"journal_article","volume":19,"publication_identifier":{"eissn":["1745-2481"],"issn":["1745-2473"]},"ec_funded":1,"status":"public"}]