{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T11:50:02Z","timestamp":1775908202917,"version":"3.50.1"},"reference-count":42,"publisher":"Cold Spring Harbor Laboratory","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2001,11,15]]},"abstract":"<jats:p>Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix\u2013loop\u2013helix transcription factor dHAND is also required for craniofacial development, and in <jats:italic>endothelin-1<\/jats:italic>(<jats:italic>ET-1<\/jats:italic>) mutant embryos, <jats:italic>dHAND<\/jats:italic> expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to <jats:italic>dHAND<\/jats:italic> transcription, we analyzed the <jats:italic>dHAND<\/jats:italic>gene for <jats:italic>cis<\/jats:italic>-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved<jats:italic>dHAND<\/jats:italic> enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from <jats:italic>endothelin receptor A<\/jats:italic>(<jats:italic>EdnrA<\/jats:italic>) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion,<jats:italic>Dlx6<\/jats:italic> was down-regulated in branchial arches from <jats:italic>EdnrA<\/jats:italic>mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and <jats:italic>dHAND<\/jats:italic> transcription during craniofacial morphogenesis.<\/jats:p>","DOI":"10.1101\/gad.931701","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T23:59:15Z","timestamp":1027727955000},"page":"3039-3049","source":"Crossref","is-referenced-by-count":133,"title":["Role of Dlx6 in regulation of an endothelin-1-dependent, <i>dHAND<\/i> branchial arch enhancer"],"prefix":"10.1101","volume":"15","author":[{"given":"Jeroen","family":"Charit\u00e9","sequence":"first","affiliation":[]},{"given":"David G.","family":"McFadden","sequence":"additional","affiliation":[]},{"given":"Giorgio","family":"Merlo","sequence":"additional","affiliation":[]},{"given":"Giovanni","family":"Levi","sequence":"additional","affiliation":[]},{"given":"David 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