This grant is aimed at studying the roles of three mouse Nkx homeodomain transcription factors, Nkx2.1, 2.2 and 6.1, in development of the basal plate of the CNS. The genes are expressed in distinct and overlapping expression patterns in the basal plate at different anterior-posterior positions. Work of Rubenstein and others have shown that all three genes are required for aspects of ventral CNS development. Dr. Rubentsein proposes to further study these three genes by carrying out a similar set of experiments for each gene. He will characterize null mutants by marker gene analysis to determine whether specification of certain cell types is altered and analyze cell proliferation, cell death and cell migration in the affected regions. He will complement these studies with gain- of-function studies by ectopically expressing the genes in early chick brain to determine whether they are sufficient to induce ventral cell types. He will also study double mutants to address overlapping gene functions and analyze in more detail expression patterns of these genes later in development and in the adult. A collaborator, Dr. Puelles, will visit the lab twice, for two months each, to help analyze the expression patterns and morphological mutant phenotypes.
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