{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:39:40Z","timestamp":1791355180787,"version":"4.3.1"},"reference-count":35,"publisher":"The Company of Biologists","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Knock-out of the mouse RXRa gene was previously shown to result in a hypoplastic heart ventricular wall, histologically detectable in 12.5 dpc fetuses. We show here that a precocious differentiation can be detected as early as 8.5 dpc in ventricular cardiomyocytes of RXR\u03b1\u2212\/\u2212 mutants. This precocious differentiation, which is characterized by the presence of striated myofibrils, sarcoplasmic reticulum and intercalated disks, is found after 9.5 dpc in about 50% of RXR\u03b1\u2212\/\u2212 subepicardial myocytes. In contrast, wild-type subepicardial myocytes remain morphologically undifferentiated up to at least 16.5 dpc. A similar precocious differentiation was observed in 9.5 dpc subepicardial myocytes of several RXR0\u03b1\u2212\/\u2212 and RAR\u03b1\u2212\/\u2212 mutants, as well as in vitamin A-deficient embryos. The proportion of differentiated subepicardial myocytes almost reached 100% in RXR\u03b1\/RXR\u03b2 double null mutants, indicating a partial functional redundancy between RXR\u03b1 and RXR\u03b2. This differentiation defect was always paralleled by a decrease in the mitotic index. In addition, subepicardial myocytes of RXR\u03b1\u2212\/\u2212, RXR\u03b1\u2212\/\u22121\/RXR\u03b2\u2212\/\u2212 or vitamin A deficient, but not of RXR\u03b2\u2212\/\u2212 and RAR\u03b1\u2212\/\u2212 embryos, were often flattened and more loosely connected to one another than those of WT embryos. Thus, retinoids are required at early stages of cardiac development to prevent differentiation, support cell proliferation and control the shape of ventricular myocytes, and both RXRs and RARs participate in the mediation of these functions.<\/jats:p>","DOI":"10.1242\/dev.124.23.4749","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T23:10:46Z","timestamp":1619392246000},"page":"4749-4758","source":"Crossref","is-referenced-by-count":153,"title":["Vitamin A deficiency and mutations of RXR\u03b1, RXR\u03b2 and RAR\u03b1 lead to early differentiation of embryonic ventricular cardiomyocytes"],"prefix":"10.1242","volume":"124","author":[{"given":"Philippe","family":"Kastner","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire , CNRS-INSERM-ULP, Coll\u00e8ge de France, BP 163, 67404 ILLKIRCH Cedex, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Messaddeq","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire , CNRS-INSERM-ULP, Coll\u00e8ge de France, BP 163, 67404 ILLKIRCH Cedex, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mark","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire , CNRS-INSERM-ULP, Coll\u00e8ge de France, BP 163, 67404 ILLKIRCH Cedex, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Wendling","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire , CNRS-INSERM-ULP, Coll\u00e8ge de France, BP 163, 67404 ILLKIRCH Cedex, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus M.","family":"Grondona","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire , CNRS-INSERM-ULP, Coll\u00e8ge de France, BP 163, 67404 ILLKIRCH Cedex, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Ghyselinck","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire , CNRS-INSERM-ULP, Coll\u00e8ge de France, BP 163, 67404 ILLKIRCH Cedex, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chambon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1997,12,1]]},"reference":[{"key":"2025021406040214100_DEVELOP_124_23_4749C1","doi-asserted-by":"publisher","first-page":"3110","DOI":"10.1073\/pnas.93.7.3110","article-title":"Developmental abnormalities in cultured mouse embryos deprived of retinoic acid by inhibition of yolk-sac retinol binding protein synthesis","volume":"93","author":"Bavik","year":"1996","journal-title":"Proc. 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