This work seeks to identify genes responsible for the developmental specification of the many cell types in the vertebrate nervous system. Most vertebrate neural cell fate decisions do not seem to depend only upon the lineage of neural cells, but instead reflect the serial recruitment of multipotential neural progenitor cells in response to tissue signals. A description of these fundamental processes is important in understanding the pathogenesis not only of developmental disorders of the brain, but also of tumors, in which such developmental control genes are often affected. Genetic studies in Drosophila show that several genes involved in cell fate decisions contain """"""""zinc finger"""""""" DNA binding motifs, which allow them to regulate transcription. Despite clues that similar genes may have important roles in vertebrates as well, the relative lack of vertebrate genetic systems makes analysis difficult. The advent of retroviral vector systems offers several strategies for elucidating the functional roles of these zinc finger genes. In this research, a family of zinc finger genes will first be identified from the mouse using the polymerae chain reaction (PCR), and then will be cloned and sequenced. Wild type, or mutated or truncated versions of these genes, will then be cloned into retroviral shuttle vectors. These vectors allow the alteration of gene expression in vitro, using specifically engineered cell lines or primary neural cultures, or in vivo in the intact retina or cerebral cortex. Cellular phenotypes of altered expression, such as transformation, alteration in proliferation rate, or persistent differentiation (or blockage of differentiation) into specific cell types, can then be determined. Once phenotypes have been observed in these experiments, the """"""""downstream"""""""" genes which are in turn regulated by the zinc-finger genes will be sought by using a modification of PCR.
