{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:46:08Z","timestamp":1770990368208,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,10,24]],"date-time":"2005-10-24T00:00:00Z","timestamp":1130112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The role of the Hedgehog signaling pathway in various aspects of gut development is still poorly understood. In the developing stomach, Sonic (Shh) and Indian (Ihh) hedgehog are expressed in both distinct and overlapping regions. Loss of Sonic hedgehog function in the stomach results in a glandular phenotype of intestinal transformation and overgrowth. These changes are reminiscent of the pre\u2010malignant lesion, intestinal metaplasia. To determine the role of Hedgehog\u2010related transcription factors, Gli2 and Gli3, in Shh signaling during stomach development, we conducted a mutant analysis of glandular stomach from <jats:italic>Shh<\/jats:italic>, <jats:italic>Gli2<\/jats:italic>, and <jats:italic>Gli3<\/jats:italic> mutant mice. Although Gli2 principally mediates the activator function of Shh, surprisingly we observed minimal changes in glandular development in the <jats:italic>Gli2<\/jats:italic> mutant stomach. Furthermore, Gli3, which typically functions as a repressor of Hedgehog signal, showed a striking phenocopy of the glandular expansion and intestinal transformation found in <jats:italic>Shh<\/jats:italic> mutant stomach. A reduction in apoptotic events was seen in all mutant stomachs with no appreciable changes in proliferation. Both <jats:italic>Shh<\/jats:italic> and <jats:italic>Gli3<\/jats:italic> mutant stomachs displayed early changes of intestinal transformation but these did not impact on the overall differentiation of the gastric epithelium. Interestingly, the observation that Gli3 shares a similar glandular phenotype to <jats:italic>Shh<\/jats:italic> mutant stomach reveals a possible novel role of Gli3 activator in the developing stomach. The embryonic stomach is a unique model of the Hedgehog pathway function and one that may help to uncover some of the mechanisms underlying the development of intestinal metaplasia. Developmental Dynamics 234:984\u2013991, 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.20542","type":"journal-article","created":{"date-parts":[[2005,10,24]],"date-time":"2005-10-24T17:16:35Z","timestamp":1130174195000},"page":"984-991","source":"Crossref","is-referenced-by-count":40,"title":["Gli3 null mice display glandular overgrowth of the developing stomach"],"prefix":"10.1002","volume":"234","author":[{"given":"Jae 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