The murine gene encoding Hox 7.1 is expressed early in the developing nervous system and shares sequence similarity with a Drosophila gene, muscle segment homeobox (msh), that functions in transcriptional regulation during Drosophila embryogenesis. These properties have led to the proposal that the protein product of Hox 7.1 (Hox 7.1) plays an integral role in directing the expression of target genes that specify neuronal phenotype. The studies outlined in this proposal will characterize the features of the Hox 7.1 polypeptide that are required for its selective interaction with regulatory elements of neuronal target genes and for transcriptional regulation. Firstly, the DNA binding properties of Hox 7.1 will be characterized using purified Hox 7.1 polypeptides. The data obtained from these analyses will represent an initial step toward elucidating the basis for the selective interaction of Hox 7.1 with DNA regulatory elements of neuronal target genes. Secondly, the transcriptional properties of Hox 7.1 will be characterized using in vitro and in vivo assay systems. The findings obtained from these studies will provide fundamental information regarding the role of Hox 7.1 in transcriptional regulation during murine neuronal development. Thirdly, polyclonal antisera specific for Hox 7.1 will be generated and these will be used to characterize the expression and biochemical properties of Hox 7.1 in the developing mouse nervous system. These studies will permit a systematic analysis of the specific brain regions and cell types that express Hox 7.1 during murine development, will define the subcellular localization of Hox 7.1 in these cells, and will identify biochemical properties of Hox 7.1, such as post-translational modifications, that are likely to have functional significance. Finally, the ultimate goal to define the function of Hox 7.1 in neurogenesis is to identify potential target genes it regulates during neuronal development; this will be the focus of the last section of this proposal. Together, the findings obtained from these studies will provide fundamental information regarding the role of Hox 7.1 in the regulation of gene expression in the developing murine CNS and will also provide general insight into the molecular mechanisms that control gene transcription during mammalian neurogenesis.
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