ENDOGENOUS RETINOIDS IN THE ZEBRAFISH EMBRYO AND ADULT

Retinoic acid and its isoforms are considered to be endogenous compoun ds which regulate embryonic development, In the work reported here we have determined which retinoids are present in zebrafish embryos and h ow 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 a s 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 th at the zebrafish embryo, like Xenopus and tunicates, contains a vast e xcess of t-retinal whereas the embryos of higher vertebrates have an e xcess of t-retinol. However, as the zebrafish grows, the levels of t-r etinol rise so that by adulthood t-retinol and t-retinal concentration s are more equivalent, indicating a changing pattern of retinoid metab olism with growth, To examine the significance of the use of t-retinal as a precursor of t-RA we treated embryos with disulphiram, an inhibi tor of retinaldehyde dehydrogenase. This resulted in embryos with an u ndulating notochord and correspondingly abnormal somites and ventral f loor plate, In contrast to this effect, 4-methylpyrazole, which inhibi ts alcohol dehydrogenases, had no effect on development. This effect o f disulphiram suggests that t-RA may be involved in the establishment of the anteroposterior axis of the embryo. (C) 1996 Wiley-Liss, Inc.