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In contrast, RXR\u03b1af1o\/RAR\u2212\/\u2212(\u03b1, \u03b2 or \u03b3) compound mutants die in utero and exhibit a large array of malformations that nearly recapitulate the full spectrum of the defects that characterize the fetal vitamin A-deficiency (VAD) syndrome. Altogether, these observations indicate that the RXR\u03b1 AF-1 region A\/B is functionally important, although less so than the ligand-dependent activation function AF-2, for efficiently transducing the retinoid signal through RAR\/RXR\u03b1 heterodimers during embryonic development. Moreover, it has a unique role in retinoic acid-dependent involution of the interdigital mesenchyme. During early placentogenesis, both the AF-1 and AF-2 activities of RXR\u03b1, \u03b2 and \u03b3 appear to be dispensable, suggesting that RXRs act as silent heterodimeric partners in this process. However, AF-2 of RXR\u03b1, but not AF-1, is required for differentiation of labyrinthine trophoblast cells, a late step in the formation of the placental barrier.<\/jats:p>","DOI":"10.1242\/dev.128.11.2049","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T05:52:33Z","timestamp":1619416353000},"page":"2049-2062","source":"Crossref","is-referenced-by-count":44,"title":["Differential contributions of AF-1 and AF-2 activities to the developmental functions of RXR\u03b1"],"prefix":"10.1242","volume":"128","author":[{"given":"Be\u0301ne\u0301dicte","family":"Mascrez","sequence":"first","affiliation":[{"name":"Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, CNRS-INSERM-ULP-Colle\u0300ge de France, BP163, 67404 Illkirch Cedex, C.U. 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, BP163, 67404 Illkirch Cedex, C.U. de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Krezel","sequence":"additional","affiliation":[{"name":"Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, CNRS-INSERM-ULP-Colle\u0300ge de France, BP163, 67404 Illkirch Cedex, C.U. de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vale\u0301rie","family":"Dupe\u0301","sequence":"additional","affiliation":[{"name":"Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, CNRS-INSERM-ULP-Colle\u0300ge de France, BP163, 67404 Illkirch Cedex, C.U. de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"LeMeur","sequence":"additional","affiliation":[{"name":"Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, CNRS-INSERM-ULP-Colle\u0300ge de France, BP163, 67404 Illkirch Cedex, C.U. 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, BP163, 67404 Illkirch Cedex, C.U. 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, BP163, 67404 Illkirch Cedex, C.U. de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042604574433200_ADAM-STITAH-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Adam-Stitah, S., Penna, L., Chambon, P. and Rochette-Egly, C. 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