title: Rdh10a Provides a Conserved Critical Step in the Synthesis of Retinoic Acid during Zebrafish Embryogenesis.
abstract: The first step in the conversion of vitamin A into retinoic acid (RA) in embryos requires retinol dehydrogenases (RDHs). Recent studies have demonstrated that RDH10 is a critical core component of the machinery that produces RA in mouse and Xenopus embryos. If the conservation of Rdh10 function in the production of RA extends to teleost embryos has not been investigated. Here, we report that zebrafish Rdh10a deficient embryos have defects consistent with loss of RA signaling, including anteriorization of the nervous system and enlarged hearts with increased cardiomyocyte number. While knockdown of Rdh10a alone produces relatively mild RA deficient phenotypes, Rdh10a can sensitize embryos to RA deficiency and enhance phenotypes observed when Aldh1a2 function is perturbed. Moreover, excess Rdh10a enhances embryonic sensitivity to retinol, which has relatively mild teratogenic effects compared to retinal and RA treatment. Performing Rdh10a regulatory expression analysis, we also demonstrate that a conserved teleost rdh10a enhancer requires Pax2 sites to drive expression in the eyes of transgenic embryos. Altogether, our results demonstrate that Rdh10a has a conserved requirement in the first step of RA production within vertebrate embryos.
authors.affiliation: The Heart Institute, Molecular Cardiovascular Biology and Developmental Biology Divisions, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
authors.forename: Enrico
authors.initials: E
authors.lastname: D'Aniello
authors.affiliation: The Heart Institute, Molecular Cardiovascular Biology and Developmental Biology Divisions, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
authors.forename: Padmapriyadarshini
authors.initials: P
authors.lastname: Ravisankar
authors.affiliation: The Heart Institute, Molecular Cardiovascular Biology and Developmental Biology Divisions, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Waxman
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006358:Hot Temperature; D017403:In Situ Hybridization; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012172:Retinaldehyde / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051762:PAX2 Transcription Factor; D029961:Zebrafish Proteins; C497320:pax2a protein, zebrafish; D014801:Vitamin A; D014212:Tretinoin; D000429:Alcohol Oxidoreductases; C000608220:retinol dehydrogenase 10a, zebrafish; C022520:retinol dehydrogenase; D012172:Retinaldehyde