{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:23:58Z","timestamp":1790760238328,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010109","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003134","name":"Fonds pour la Formation \u00e0 la Recherche dans l\u2019Industrie et dans l\u2019Agriculture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003134","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cr\u00e9dits Sectoriels de Recherche en Sciences de la Sant\u00e9"},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ARC -Uliege"},{"name":"Fonds National pour la Recherche Scientifique"},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["CDR"],"award-info":[{"award-number":["CDR"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006673","name":"Fonds L\u00e9on Fredericq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006673","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fonds speciaux Uliege"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    ARP\/ASCL transcription factors are key determinants of cell fate specification in a wide variety of tissues, coordinating the acquisition of generic cell fates and of specific subtype identities. How these factors, recognizing highly similar DNA motifs, display specific activities, is not yet fully understood. To address this issue, we overexpressed different ARP\/ASCL factors in zebrafish\n                    <jats:italic>ascl1a<\/jats:italic>\n                    -\/- mutant embryos to determine which ones are able to rescue the intestinal secretory lineage. We found that Ascl1a\/b, Atoh1a\/b and Neurod1 factors are all able to trigger the first step of the secretory regulatory cascade but distinct secretory cells are induced by these factors. Indeed, Neurod1 rescues the enteroendocrine lineage while Ascl1a\/b and Atoh1a\/b rescue the goblet cells. Gain-of-function experiments with Ascl1a\/Neurod1 chimeric proteins revealed that the functional divergence is encoded by a 19-aa ultra-conserved element (UCE), present in all Neurod members but absent in the other ARP\/ASCL proteins. Importantly, inserting the UCE into the Ascl1a protein reverses the rescuing capacity of this Ascl1a chimeric protein that cannot rescue the goblet cells anymore but can efficiently rescue the enteroendocrine cells. This novel domain acts indeed as a goblet cell fate repressor that inhibits\n                    <jats:italic>gfi1aa<\/jats:italic>\n                    expression, known to be important for goblet cell differentiation. Deleting the UCE domain of the endogenous Neurod1 protein leads to an increase in the number of goblet cells concomitant with a reduction of the enteroendocrine cells, phenotype also observed in the\n                    <jats:italic>neurod1<\/jats:italic>\n                    null mutant. This highlights the crucial function of the UCE domain for NeuroD1 activity in the intestine. As Gfi1 acts as a binary cell fate switch in several tissues where Neurod1 is also expressed, we can envision a similar role of the UCE in other tissues, allowing Neurod1 to repress Gfi1 to influence the balance between cell fates.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1010109","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T13:52:21Z","timestamp":1647265941000},"page":"e1010109","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification of an evolutionarily conserved domain in Neurod1 favouring enteroendocrine versus goblet cell fate"],"prefix":"10.1371","volume":"18","author":[{"given":"Anne 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