The central nervous system (CNS) consists of a diverse set of nerve cells. Neurogenesis is the process in which these nerve cells are formed and attain their unique cell fates. The subject of this proposal is to identify and analyse the function of genes involved in neurogenesis. Drosophila melanogaster is an excellent system to investigate the molecular mechanisms of CNS formation because of the powerful genetic, molecular, and cellular techniques that can be utilized. We will focus our attention on the development of a specific set of nerve cells, those that lie along the midline of the CNS, and identify and study the genes that function in their formation. Our previous molecular and cellular studies have shown that the single-minded (sim) gene plays an important role in determination of cell fate of the precursors of the midline group of cells. In this proposal, the structure, expression of the different sim transcripts and gene products, and their role in neurogenesis will be investigated. Experiments will also seek to understand the mechanisms that control the specificity of gene expression during formation of the CNS. Additional genes with sequence similarity to sim in both Drosophila and vertebrates will be identified by low-stringency hybridization techniques. Genetic and molecular methods will be used to isolate novel genes that are involved in the development of the midline group of cells. This will include a genetic screen in which mutant strains are directly examined for defects in the midline nerve cells. Another genetic screen will seek mutants that interact with the sim gene. A third method involves the use of genomic insertion elements to identify genes expressed along the midline. The work proposed will begin to reveal the molecular mechanisms that control the formation of the CNS. Thus, it is likely to be relevant in better understanding the development of the human CNS, and in the study of certain mental disorders and disease.
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