{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:59:31Z","timestamp":1791892771681,"version":"4.3.4"},"reference-count":50,"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>\n               <jats:p>Pancreas organogenesis is regulated by the interaction of distinct signaling pathways that promote or restrict morphogenesis and cell differentiation. Previous work has shown that activin, a TGF\u03b2 signaling molecule, permits pancreas development by repressing expression of Sonic hedgehog (Shh), a member of the hedgehog family of signaling molecules that antagonize pancreas development. Here we show that Indian hedgehog (Ihh), another hedgehog family member, and Patched 1 (Ptc1), a receptor and negative regulator of hedgehog activity, are expressed in pancreatic tissue. Targeted inactivation of Ihh in mice allows ectopic branching of ventral pancreatic tissue resulting in an annulus that encircles the duodenum, a phenotype frequently observed in humans suffering from a rare disorder known as annular pancreas. Shh\u2212\/\u2212and Shh\u2212\/\u2212Ihh+\/\u2212 mutants have a threefold increase in pancreas mass, and a fourfold increase in pancreatic endocrine cell numbers. In contrast, mutations in Ptc1 reduce pancreas gene expression and impair glucose homeostasis. Thus, islet cell, pancreatic mass and pancreatic morphogenesis are regulated by hedgehog signaling molecules expressed within and adjacent to the embryonic pancreas. Defects in hedgehog signaling may lead to congenital pancreatic malformations and glucose intolerance.<\/jats:p>","DOI":"10.1242\/dev.127.22.4905","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T04:20:15Z","timestamp":1619410815000},"page":"4905-4913","source":"Crossref","is-referenced-by-count":340,"title":["Regulation of pancreas development by hedgehog signaling"],"prefix":"10.1242","volume":"127","author":[{"given":"Matthias","family":"Hebrok","sequence":"first","affiliation":[{"name":"Harvard University 1 Department of Molecular and Cellular Biology and Howard Hughes Medical Institute , , 7 Divinity Avenue, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Harvard University 1 Department of Molecular and Cellular Biology and Howard Hughes Medical Institute , , 7 Divinity Avenue, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"St-Jacques","sequence":"additional","affiliation":[{"name":"Harvard University 2 Department of Molecular and Cellular Biology, The Biolabs , , 16 Divinity Avenue, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"McMahon","sequence":"additional","affiliation":[{"name":"Harvard University 2 Department of Molecular and Cellular Biology, The Biolabs , , 16 Divinity Avenue, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Melton","sequence":"additional","affiliation":[{"name":"Harvard University 1 Department of Molecular and Cellular Biology and Howard Hughes Medical Institute , , 7 Divinity Avenue, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2000,11,15]]},"reference":[{"key":"2023030307455096300_","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/385257a0","article-title":"Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells","volume":"385","author":"Ahlgren","year":"1997","journal-title":"Nature"},{"key":"2023030307455096300_","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/S0960-9822(06)00340-X","article-title":"Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas","volume":"7","author":"Apelqvist","year":"1997","journal-title":"Curr. 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