The genetic mechanisms of the central nervous system (CNS) patterning occuring during early ontogenesis are still poorly understood. (i) Members of the fork head (fkh) family of genes share homology at the level of a novel DNA-binding motif coding sequence and some have been demonstrated to regulate axis formation. I propose to further study a putative new mouse member to elucidate its function in pattern formation by using gene targeting procedures. (ii) Pax-3 and Pax-6 are transcription factors expressed in the embryonic CNS under the regulation of signals controlling the neural tube polarity. Drosophila, rat, mouse and human mutant studies indicate that they are important morphoregulators. In order to study their function in CNS patterning and cell differentitation, I propose to analyse the effects of ectopic expression of the Pax-3 and Pax-6 genes in the CNS under the regulation of the En-2 and Wnt-l gene promoter/enhancer.