{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:15:56Z","timestamp":1785467756824,"version":"3.56.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Fetal Alcohol Spectrum Disorder (FASD) arises from maternal consumption of alcohol during pregnancy affecting 2%\u20135% of the Western population. In <jats:italic>Xenopus laevis<\/jats:italic> studies, we showed that alcohol exposure during early gastrulation reduces retinoic acid (RA) levels at this critical embryonic stage inducing craniofacial malformations associated with Fetal Alcohol Syndrome. A genetic mouse model that induces a transient RA deficiency in the node during gastrulation is described. These mice recapitulate the phenotypes characteristic of prenatal alcohol exposure (PAE) suggesting a molecular etiology for the craniofacial malformations seen in children with FASD. <jats:italic>Gsc<\/jats:italic><jats:sup><jats:italic>+\/Cyp26A1<\/jats:italic><\/jats:sup> mouse embryos have a r<jats:italic>educ<\/jats:italic>ed RA domain and expression in the developing frontonasal prominence regi<jats:italic>on<\/jats:italic> and delayed <jats:italic>HoxA1<\/jats:italic> and <jats:italic>HoxB1<\/jats:italic> expression at E8.5. These embryos also show aberrant neurofilament expression during cranial nerve formation at E10.5 and have significant FASD sentinel-like craniofacial phenotypes at E18.5. <jats:italic>Gsc<\/jats:italic><jats:sup><jats:italic>+\/Cyp26A1<\/jats:italic><\/jats:sup> mice develop severe maxillary malocclusions in adulthood. Phenocopying the PAE-induced developmental malformations with a genetic model inducing RA deficiency during early gastrulation strongly supports the alcohol\/vitamin A competition model as a major molecular etiology for the neurodevelopmental defects and craniofacial malformations seen in children with FASD.<\/jats:p>","DOI":"10.3389\/fcell.2023.1208279","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T04:51:27Z","timestamp":1686891087000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetically programmed retinoic acid deficiency during gastrulation phenocopies most known developmental defects due to acute prenatal alcohol exposure in FASD"],"prefix":"10.3389","volume":"11","author":[{"given":"B.","family":"Petrelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ozt\u00fcrk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Pind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Ayele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Fainsod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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