The glucose dehydrogenase gene (Gld) in Drosophila will be used to investigate the contribution and interaction of three factor which determine regulatory fates: functional needs, cellular determination/differentiation, and the evolutionary history of the regulatory system. The developmental pattern of Gld expression has been exhaustively studies and exhibits a number of characteristics which make it an ideal regulatory paradigm. The cis-acting regulatory elements responsible for the following properties of Gld expression will be determined: ecdysterone mediated induction, epidermal restriction, and adult male-limited expression. The evolutionary and developmental aspects of the adult male-limited expression will be investigated among three Drosophila species which exhibit different patterns of expression at the adult stage. These studies will involve further characterization of Gld expression in the developing reproductive organs, the control of this expression by the sex determination genes, and the characterization of the promoter differences between the species via P-element transformation. Moreover, the hypothesis that the male fertility function of the Gld gene is independent of GLD enzyme activity will be tested. Lastly, a number of studies are proposed to further characterize the Gld YYRR box. These include testing for YYRR box function, characterizing a YYRR box binding protein, mapping the cytogenetic location of the other boxes in the Drosophila genome, and isolating a few other YYRR box-containing genes. The long-term goal of this project is two-fold, to provide a description of the mechanisms underlying the control of gene expression and, more importantly, to understand why genes are expressed in terms of the underlying developmental and evolutionary forces which shape the regulatory circuitry. Determining not only how, but why genes are expressed is essential for understanding human diseases caused by misregulation of gene expression.
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