V-ERBA AND CITRAL REDUCE THE TERATOGENIC EFFECTS OF ALL-TRANS-RETINOIC ACID AND RETINOL, RESPECTIVELY, IN XENOPUS EMBRYOGENESIS

Treatment of late blastula/early gastrula stage Xenopus embryos with a ll-trans retinoic acid results in disruption of the primary body axis through effects on both mesoderm and neuroectoderm. This effect of ret inoic acid, coupled with the known presence of retinoic acid in Xenopu s embryos has led to the proposal that retinoic acid may be an endogen ous morphogen providing positional information in early development. T o further elucidate the role of retinoic acid in early Xenopus develop ment, we have attempted to interfere with the retinoic acid signalling pathway both at the level of retinoic acid formation, by treatment wi th citral (3,7-dimethy-2,6-octadienal), and at the level of nuclear re tinoic acid receptor function, by microinjection of v-erbA mRNA. The f easibility of this approach was demonstrated by the ability of citral treatment and v-erbA mRNA injection to reduce the teratogenic effects of exogenous retinol and retinoic acid, respectively, in early Xenopus development. Interestingly, v-erbA mRNA injection and citral treatmen t of gastrula stage embryos resulted in tadpoles with a similar set of developmental defects. The defects were chiefly found in tissues that received a contribution of cells from the neural crest, suggesting th at at least a subset of neural crest cells may be sensitive to the end ogenous level of retinoic acid. In accord with this proposal, it was f ound that the expression patterns of two early markers of cranial neur al crest cells, Xtwi and XAP-2, were altered in embryos injected with v-erbA mRNA. These results indicate that structures in addition to the primary axis are regulated by retinoic acid signalling during early X enopus development.