title: Endogenous retinoids in the zebrafish embryo and adult.
abstract: Retinoic acid and its isoforms are considered to be endogenous compounds which regulate embryonic development. In the work reported here we have determined which retinoids are present in zebrafish embryos and how their levels change throughout development and into adulthood. All-trans-RA is present and its level does not change significantly during embryogenesis. We failed to detect other retinoic acid isomers such as 9-cis-RA and 4-oxo-RA, but we did observe a rapid rise in the level of didehydroretinol after gastrulation. The most striking result is that the zebrafish embryo, like Xenopus and tunicates, contains a vast excess of t-retinal whereas the embryos of higher vertebrates have an excess of t-retinol. However, as the zebrafish grows, the levels of t-retinol rise so that by adulthood t-retinol and t-retinal concentrations are more equivalent, indicating a changing pattern of retinoid metabolism with growth. To examine the significance of the use of t-retinal as a precursor of t-RA we treated embryos with disulphiram, an inhibitor of retinaldehyde dehydrogenase. This resulted in embryos with an undulating notochord and correspondingly abnormal somites and ventral floor plate. In contrast to this effect, 4-methylpyrazole, which inhibits alcohol dehydrogenases, had no effect on development. This effect of disulphiram suggests that t-RA may be involved in the establishment of the anteroposterior axis of the embryo.
authors.affiliation: Developmental Biology Research Centre, King's College London, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Costaridis
authors.forename: C
authors.initials: C
authors.lastname: Horton
authors.forename: J
authors.initials: J
authors.lastname: Zeitlinger
authors.forename: N
authors.initials: N
authors.lastname: Holder
authors.forename: M
authors.initials: M
authors.lastname: Maden
mesh_terms: D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000077604:Fomepizole; D007150:Immunohistochemistry; D011720:Pyrazoles / Q000494:pharmacology; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D013237:Stereoisomerism; D014212:Tretinoin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000963:Antimetabolites; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D012176:Retinoids; C024366:vitamin A2; D014801:Vitamin A; C002202:4-oxoretinoic acid; D014212:Tretinoin; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde; D004221:Disulfiram