{"date_published":"2024-10-14T00:00:00Z","doi":"10.1371/journal.pcbi.1012508","language":[{"iso":"eng"}],"quality_controlled":"1","has_accepted_license":"1","publication_status":"published","department":[{"_id":"AnKi"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"external_id":{"pmid":["39401260"]},"publication_identifier":{"issn":["1553-734X"],"eissn":["1553-7358"]},"ddc":["570"],"scopus_import":"1","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.","status":"public","oa_version":"Published Version","project":[{"_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa","name":"Mechanisms of tissue size regulation in spinal cord development","grant_number":"101044579"}],"intvolume":"        20","date_updated":"2024-10-29T12:20:58Z","pmid":1,"article_type":"original","date_created":"2024-10-27T23:01:45Z","OA_place":"publisher","DOAJ_listed":"1","publisher":"Public Library of Science","author":[{"full_name":"Ho, Richard D.J.G.","first_name":"Richard D.J.G.","last_name":"Ho"},{"last_name":"Kishi","id":"3065DFC4-F248-11E8-B48F-1D18A9856A87","full_name":"Kishi, Kasumi","first_name":"Kasumi"},{"last_name":"Majka","full_name":"Majka, Maciej","first_name":"Maciej"},{"last_name":"Kicheva","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","first_name":"Anna","orcid":"0000-0003-4509-4998","full_name":"Kicheva, Anna"},{"full_name":"Zagórski, Marcin P","first_name":"Marcin P","orcid":"0000-0001-7896-7762","last_name":"Zagórski","id":"343DA0DC-F248-11E8-B48F-1D18A9856A87"}],"corr_author":"1","type":"journal_article","article_number":"e1012508","file":[{"date_updated":"2024-10-29T11:59:09Z","access_level":"open_access","success":1,"file_size":3732443,"file_name":"2024_PloSComBio_Ho.pdf","creator":"dernst","file_id":"18487","relation":"main_file","content_type":"application/pdf","date_created":"2024-10-29T11:59:09Z","checksum":"42fa714459943cb3961b40fab8fd82c8"}],"oa":1,"year":"2024","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"}],"month":"10","OA_type":"gold","title":"Dynamics of morphogen source formation in a growing tissue","file_date_updated":"2024-10-29T11:59:09Z","_id":"18481","license":"https://creativecommons.org/licenses/by/4.0/","day":"14","article_processing_charge":"No","citation":{"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.","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>","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.","short":"R.D.J.G. Ho, K. Kishi, M. Majka, A. Kicheva, M.P. Zagórski, PLoS Computational Biology 20 (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>.","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>."},"publication":"PLoS Computational Biology","volume":20}