{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:49:07Z","timestamp":1790718547076,"version":"4.1.0"},"reference-count":61,"publisher":"The Company of Biologists","issue":"16","license":[{"start":{"date-parts":[[1998,8,15]],"date-time":"1998-08-15T00:00:00Z","timestamp":903139200000},"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":[[1998,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived branchial arches and branchial arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the branchial arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the branchial arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the branchial and aortic arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second arches are hypoplastic secondary to programmed cell death and the third and fourth arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the branchial arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null branchial arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal branchial arch. Complete disruption of this molecular pathway results in growth failure of the branchial arches from apoptosis, while partial disruption leads to defects of branchial arch derivatives, similar to those seen in CATCH-22 syndrome.<\/jats:p>","DOI":"10.1242\/dev.125.16.3005","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:22:37Z","timestamp":1619407357000},"page":"3005-3014","source":"Crossref","is-referenced-by-count":229,"title":["A signaling cascade involving endothelin-1, dHAND and Msx1 regulates development of neural-crest-derived branchial arch mesenchyme"],"prefix":"10.1242","volume":"125","author":[{"given":"Tiffani","family":"Thomas","sequence":"first","affiliation":[{"name":"1 Department of Pediatrics, Division of Cardiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kurihara","sequence":"additional","affiliation":[{"name":"3 The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"1 Department of Pediatrics, Division of Cardiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Kurihara","sequence":"additional","affiliation":[{"name":"3 The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Yazaki","sequence":"additional","affiliation":[{"name":"3 The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric N.","family":"Olson","sequence":"additional","affiliation":[{"name":"2 Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75235-9148, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Srivastava","sequence":"additional","affiliation":[{"name":"1 Department of Pediatrics, Division of Cardiology"},{"name":"2 Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75235-9148, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1998,8,15]]},"reference":[{"key":"2025021501325174300_DEVELOP_125_16_3005C1","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/S0168-9525(97)01187-6","article-title":"Cellular and molecular biology of neural crest lineage determination","volume":"13","author":"Anderson","year":"1997","journal-title":"Trends Genet"},{"key":"2025021501325174300_DEVELOP_125_16_3005C2","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/0092-8674(94)90018-3","article-title":"Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons","volume":"79","author":"Baynash","year":"1994","journal-title":"Cell"},{"key":"2025021501325174300_DEVELOP_125_16_3005C3","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1101\/gad.11.11.1357","article-title":"Homeodomain factor Nkx2-5 controls left\/right asymmetric expression of bHLH gene eHand during murine heart development","volume":"11","author":"Biben","year":"1997","journal-title":"Genes Dev"},{"key":"2025021501325174300_DEVELOP_125_16_3005C4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1006\/excr.1995.1173","article-title":"Origins and developmental potential of the neural crest","volume":"218","author":"Bronner-Fraser","year":"1995","journal-title":"Exp. 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