The role of retinoic acid in the spatiotemporal patterning of dorsal embryonic hindbrain. (360G-Wellcome-080019_Z_06_Z)

We will investigate how retinoic acid influences the development of late-born dorsal structures in the hindbrain. These comprise both the cerebellum and the precerebellar and noradrenergic neurons of the hindbrain. From preliminary evidence we believe retinoic acid plays a role in both the induction and maintenance of these vital nuclei. To test this hypothesis, we have devised a comprehensive programme of research utilizing avian and mammalian models to accomplish four aims. We will 1) fully ch aracterize the expression of retinoic acid pathway members in the late hindbrain. Using both molecular markers and the analysis of neuronal migration and projections, we will then test the effects of 2) blocking retinoic acid receptors through overexpression of dominant negative constructs (chick) or targeted conditional knock-outs (mouse). In a complementary strategy we will, 3) focally block the production of retinoic acid by transplantation of quail material from Vitamin A deprived embryos in to chick hosts. Finally 4), we will examine the long-term dependence of these cell groups on choroid plexus derived retinoic acid using a Vitamin A deficiency model.