NOVEL RETINOIC ACID RECEPTOR LIGANDS IN XENOPUS EMBRYOS

Retinoids are a large family of natural and synthetic compounds relate d to vitamin A that have pleiotropic effects on body physiology, repro duction, immunity, and embryonic development. The diverse activities o f retinoids are primarily mediated by two families of nuclear retinoic acid receptors, the RARs and RXRs. Retinoic acids are thought to be t he only natural ligands for these receptors and are widely assumed to be the active principle of vitamin A. However, during an unbiased, bio activity-guided fractionation ofXenopus embryos, we were unable to det ect significant levels of all-trans or 9-cis retinoic acids. Instead, we found that the major bioactive retinoid in the Xenopus egg and earl y embryo is 4-oxoretinaldehyde, which is capable of binding to and tra nsactivating RARs. In addition to its inherent activity, 4-oxoretinald ehyde appears to be a metabolic precursor of two other RAR ligands, 4- oxoretinoic acid and 4-oxoretinol. The remarkable increase in activity of retinaldehyde and retinol as a consequence of 3-oxo derivatization suggests that this metabolic step could serve a critical regulatory f unction during embryogenesis.