{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:27:06Z","timestamp":1791890826637,"version":"4.3.4"},"reference-count":46,"publisher":"The Company of Biologists","issue":"22","license":[{"start":{"date-parts":[[2000,11,15]],"date-time":"2000-11-15T00:00:00Z","timestamp":974246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The midgut and hindgut endoderm of the mouse embryo give rise to the intestinal epithelium, yet it is not known how the intestinal program is chosen in contrast to other endoderm-derived cell types. Previous tissue explant studies with embryos at 8.5 to 11.5 days gestation (d) showed that when the gut mesoderm is removed from the prospective intestinal endoderm, the endoderm activates the expression of liver-specific genes such as serum albumin, demonstrating the endoderm\u2019s pluripotence. This reversible repression of liver genes does not affect the expression of the endodermal transcription factors HNF3 and GATA4, nor these factors\u2019 ability to engage target sites in chromatin. We have now found that at 13.5 d, the mesoderm gains a second inhibitory activity, resulting in the irreversible loss of expression of HNF3 (Foxa2) and GATA factors in the endoderm and the absence of factors binding to their target sites in chromatin. The second inhibitory activity causes the endoderm to lose the potential to activate a liver gene, and this restriction precedes the normal cytodifferentiation of the intestinal epithelium. In summary, two inhibitory interactions with mesoderm successively restrict the developmental potential of the gut endoderm, leading to intestinal differentiation. We also observed rare gut bud structures in midgestation embryos that appear to represent murine examples of Meckel\u2019s Diverticulum, a congenital abnormality in human development. The absence of restrictive mesodermal interactions could explain how Meckel\u2019s diverticula express diverse non-intestinal, endoderm-derived cell types.<\/jats:p>","DOI":"10.1242\/dev.127.22.4915","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T04:20:54Z","timestamp":1619410854000},"page":"4915-4923","source":"Crossref","is-referenced-by-count":67,"title":["Repressive and restrictive mesodermal interactions with gut endoderm: possible relation to Meckel\u2019s Diverticulum"],"prefix":"10.1242","volume":"127","author":[{"given":"Pascale","family":"Bossard","sequence":"first","affiliation":[{"name":"Cell and Developmental Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth S.","family":"Zaret","sequence":"additional","affiliation":[{"name":"Cell and Developmental Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2000,11,15]]},"reference":[{"key":"2023030307455600500_","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/0092-8674(94)90522-3","article-title":"HNF-3\u03b2 is essential for node and notochord formation in mouse development","volume":"78","author":"Ang","year":"1994","journal-title":"Cell"},{"key":"2023030307455600500_","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1242\/dev.119.4.1301","article-title":"The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3\/forkhead proteins","volume":"119","author":"Ang","year":"1993","journal-title":"Development"},{"key":"2023030307455600500_","first-page":"2235","article-title":"Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart","volume":"13","author":"Arceci","year":"1993","journal-title":"Mol. 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