{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:52:11Z","timestamp":1791975131910,"version":"4.4.0"},"reference-count":0,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medical Research Council","award":["MR\/V002163\/1"],"award-info":[{"award-number":["MR\/V002163\/1"]}]},{"name":"Medical Research Council","award":["MR\/Y013476\/1"],"award-info":[{"award-number":["MR\/Y013476\/1"]}]},{"name":"Horizon 2020 Framework Programme","award":["H2020-EU.1.2.2"],"award-info":[{"award-number":["H2020-EU.1.2.2"]}]},{"name":"Wellcome Trust","award":["224070\/Z\/21\/Z"],"award-info":[{"award-number":["224070\/Z\/21\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Biotechnology and Biological Sciences Research Council","award":["White Rose Mechanistic Biology DTP studentship"],"award-info":[{"award-number":["White Rose Mechanistic Biology DTP studentship"]}],"id":[{"id":"https:\/\/ror.org\/00cwqg982","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Sheffield","award":["Strategic Research Fellowship in the Physics of Life and Quantitative Biology"],"award-info":[{"award-number":["Strategic Research Fellowship in the Physics of Life and Quantitative Biology"]}],"id":[{"id":"https:\/\/ror.org\/05krs5044","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The enteric nervous system (ENS) is the main branch of the peripheral nervous system that innervates the gastrointestinal tract controlling vital functions. It arises during embryogenesis via migration, proliferation and differentiation of neural crest-derived ENS progenitors. Perturbation of these processes, caused by mutations in key signalling pathway components and transcription factors, prevents progenitor colonisation of the distal gut causing aganglionic phenotypes and enteric neuropathies such as Hirschsprung (HSCR) disease. While animal models implicate Notch signalling in ENS specification, its role in human ENS progenitor cell fate decisions remains unclear. Here, we employ a human pluripotent stem cell-based model to show that Notch signalling is a key regulator of human ENS progenitor dynamics. Quantitative modelling of our in vitro data indicates that Notch inhibition accelerates progenitor differentiation without substantially altering neuronal versus glial lineage bias. Furthermore, we establish that Notch signalling controls human ENS progenitor migration by influencing migration velocity and directionality. Together, these findings provide mechanistic insights into how Notch signalling disruption may contribute to the pathogenesis of human intestinal aganglionosis.<\/jats:p>","DOI":"10.1242\/dev.205775","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:26:48Z","timestamp":1791973608000},"source":"Crossref","is-referenced-by-count":0,"title":["Notch signalling governs human enteric nervous system progenitor dynamics"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-2426","authenticated-orcid":false,"given":"Antigoni","family":"Gogolou","sequence":"first","affiliation":[{"name":"1 Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield S10 2TN, UK"},{"name":"2 Neuroscience Institute, The University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7311-4977","authenticated-orcid":false,"given":"Nikolas","family":"Stefanidis","sequence":"additional","affiliation":[{"name":"1 Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield S10 2TN, UK"},{"name":"3 School of Mathematical and Physical Sciences, University of Sheffield, Hicks Building, Hounsfield Road, Sheffield, S3 7RH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-619X","authenticated-orcid":false,"given":"Fay","family":"Cooper","sequence":"additional","affiliation":[{"name":"1 Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield S10 2TN, UK"},{"name":"2 Neuroscience Institute, The University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9295-237X","authenticated-orcid":false,"given":"Guillaume","family":"Blin","sequence":"additional","affiliation":[{"name":"4 Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, Edinburgh, UK"},{"name":"5 Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0273-0835","authenticated-orcid":false,"given":"Stanley E.","family":"Strawbridge","sequence":"additional","affiliation":[{"name":"1 Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield S10 2TN, UK"},{"name":"6 Bateson Centre for Disease Mechanisms, University of Sheffield, Sheffield, UK"},{"name":"7 Insigneo Institute, University of Sheffield, Sheffield S10 2TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0525-4336","authenticated-orcid":false,"given":"Alexander G.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"2 Neuroscience Institute, The University of Sheffield, Sheffield S10 2TN, UK"},{"name":"3 School of Mathematical and Physical Sciences, University of Sheffield, Hicks Building, Hounsfield Road, Sheffield, S3 7RH, UK"},{"name":"7 Insigneo Institute, University of Sheffield, Sheffield S10 2TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2184-2990","authenticated-orcid":false,"given":"Anestis","family":"Tsakiridis","sequence":"additional","affiliation":[{"name":"1 Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield S10 2TN, UK"},{"name":"2 Neuroscience Institute, The University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,10,14]]},"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.205775\/3721370\/dev205775.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.205775\/3721370\/dev205775.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:26:50Z","timestamp":1791973610000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/doi\/10.1242\/dev.205775\/373168\/Notch-signalling-governs-human-enteric-nervous"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1242\/dev.205775","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"article-number":"dev.205775"}}