{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:25:01Z","timestamp":1790861101125,"version":"4.1.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,7,3]]},"abstract":"<jats:p>Wnt signaling is required for the maintenance of intestinal stem cells and self-renewal of the intestinal epithelium. Intestinal cancers are frequently associated with mutations that activate the Wnt pathway. The role of Wnt signaling on differentiation of lineage-specific precursors in the intestine is not well characterized. Here, we show that specification of enteroendocrine but not Paneth cells occurs independently of Wnt signals by conditional deletion of \u03b2-catenin in immature cells expressing the transcription factor, neurogenin 3. In addition, we determined whether neurogenin 3-expressing cells respond to abnormal Wnt signaling. Activation of the Wnt pathway by conditionally deleting exon 3 of the \u03b2-catenin gene at an early stage of enteroendocrine cell differentiation induced small-intestinal adenomas expressing serotonin, a feature not previously described in other tumors induced by Wnt in mice. In contrast, excision of exon 3 of \u03b2-catenin at a later stage of enteroendocrine differentiation did not produce tumors. These results provide direct evidence that some intestinal lineages are specified independently of the Wnt pathway and may lead to a better understanding of the spectrum of neuroendocrine differentiation frequently seen in human gastrointestinal cancer.<\/jats:p>","DOI":"10.1073\/pnas.0702665104","type":"journal-article","created":{"date-parts":[[2007,6,25]],"date-time":"2007-06-25T21:05:26Z","timestamp":1182805526000},"page":"11328-11333","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":49,"title":["Enteroendocrine precursors differentiate independently of Wnt and form serotonin expressing adenomas in response to active \u03b2-catenin"],"prefix":"10.1073","volume":"104","author":[{"given":"Yang","family":"Wang","sequence":"first","affiliation":[{"name":"*Division of Gastroenterology, GRASP Digestive Disease Center, Tufts\u2013New England Medical Center, Boston, MA 02111; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryann","family":"Giel-Moloney","sequence":"additional","affiliation":[{"name":"*Division of Gastroenterology, GRASP Digestive Disease Center, Tufts\u2013New England Medical Center, Boston, MA 02111; 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