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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Genetics Study Section (GEN)
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Vanderbilt University Medical Center
Schools of Arts and Sciences
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Keplinger, B L; Guo, X; Quine, J et al. (2001) Complex organization of promoter and enhancer elements regulate the tissue- and developmental stage-specific expression of the Drosophila melanogaster Gld gene. Genetics 157:699-716
Olsen, D S; Jordan, B; Chen, D et al. (1998) Isolation of the gene encoding the Drosophila melanogaster homolog of the Saccharomyces cerevisiae GCN2 eIF-2alpha kinase. Genetics 149:1495-509
Keplinger, B L; Rabetoy, A L; Cavener, D R (1996) A somatic reproductive organ enhancer complex activates expression in both the developing and the mature Drosophila reproductive tract. Dev Biol 180:311-23
Gunaratne, P; Ross, J L; Zhang, Q et al. (1994) An evolutionarily conserved palindrome in the Drosophila Gld promoter directs tissue-specific expression. Proc Natl Acad Sci U S A 91:2738-42
Ross, J L; Fong, P P; Cavener, D R (1994) Correlated evolution of the cis-acting regulatory elements and developmental expression of the Drosophila Gld gene in seven species from the subgroup melanogaster. Dev Genet 15:38-50
Quine, J A; Gunaratne, P; Organ, E L et al. (1993) Tissue-specific regulatory elements of the Drosophila Gld gene. Mech Dev 42:3-13
Cavener, D R (1992) GMC oxidoreductases. A newly defined family of homologous proteins with diverse catalytic activities. J Mol Biol 223:811-4
Schiff, N M; Feng, Y; Quine, J A et al. (1992) Evolution of the expression of the Gld gene in the reproductive tract of Drosophila. Mol Biol Evol 9:1029-49
Schonbaum, C P; Organ, E L; Qu, S et al. (1992) The Drosophila melanogaster stranded at second (sas) gene encodes a putative epidermal cell surface receptor required for larval development. Dev Biol 151:431-45
Cavener, D R; Ray, S C (1991) Eukaryotic start and stop translation sites. Nucleic Acids Res 19:3185-92

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