{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:22:14Z","timestamp":1791408134652,"version":"4.3.3"},"reference-count":93,"publisher":"The Company of Biologists","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,5,15]]},"abstract":"<jats:p>Fusion and hypoplasia of the first two branchial arches, a defect typically observed in retinoic acid (RA) embryopathy, is generated in cultured mouse embryos upon treatment with BMS453, a synthetic compound that exhibits retinoic acid receptor \u03b2 (RAR\u03b2) agonistic properties in transfected cells. By contrast, no branchial arch defects are observed following treatment with synthetic retinoids that exhibit RAR\u03b1 or RAR\u03b3 agonistic properties. The BMS453-induced branchial arch defects are mediated through RAR activation, as they are similar to those generated by a selective pan-RAR agonist, are prevented by a selective pan-RAR antagonist and cannot be mimicked by exposure to a pan-RXR agonist alone. They are enhanced in the presence of a pan-RXR agonist, and cannot be generated in Rarb-null embryos. Furthermore, they are accompanied, in the morphologically altered region, by ectopic expression of Rarb and of several other direct RA target genes. Therefore, craniofacial abnormalities characteristic of the RA embryopathy are mediated through ectopic activation of RAR\u03b2\/RXR heterodimers, in which the ligand-dependent activity of RXR is subordinated to that of RAR\u03b2. Endodermal cells lining the first two branchial arches respond to treatment with the RAR\u03b2 agonist, in contrast to neural crest cells and ectoderm, which suggests that a faulty endodermal regionalization is directly responsible for RA-induced branchial arch dysmorphologies. Additionally, we provide the first in vivo evidence that the synthetic RAR\u03b2 agonist BMS453 exhibits an antagonistic activity on the two other RAR isotypes.<\/jats:p>","DOI":"10.1242\/dev.00428","type":"journal-article","created":{"date-parts":[[2003,3,31]],"date-time":"2003-03-31T16:53:46Z","timestamp":1049129626000},"page":"2083-2093","source":"Crossref","is-referenced-by-count":98,"title":["Retinoic acid-induced developmental defects are mediated by RAR\u03b2\/RXR heterodimers in the pharyngeal endoderm"],"prefix":"10.1242","volume":"130","author":[{"given":"Nicolas","family":"Matt","sequence":"first","affiliation":[{"name":"Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, CNRS\/INSERM\/ULP, Colle\u0300ge de France, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert B.","family":"Ghyselinck","sequence":"additional","affiliation":[{"name":"Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, CNRS\/INSERM\/ULP, Colle\u0300ge de France, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Wendling","sequence":"additional","affiliation":[{"name":"Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, CNRS\/INSERM\/ULP, Colle\u0300ge de France, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chambon","sequence":"additional","affiliation":[{"name":"Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, CNRS\/INSERM\/ULP, Colle\u0300ge de France, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mark","sequence":"additional","affiliation":[{"name":"Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, CNRS\/INSERM\/ULP, Colle\u0300ge de France, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042611463349500_REF1","doi-asserted-by":"crossref","unstructured":"Alles, A. 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