• Forte, Michael (PI)

Project: Research project

Project Details


DESCRIPTION: The objective of this proposal is to define how the activation of the G protein Gs alpha subunit (DGs) in Drosophila impacts on the development and function of a specific cell type using wing blistering as a paradigm. The investigator, using a sophisticated in vivo expression system based on GAL4 control elements, has noted that the expression of an activated mutant of DGs (DGs*) results in numerous and complex phenotypes. One of the simplest and most consistently observed is the formation of wing blisters by GAL4 lines that mediate expression in wing epithelium during late pupal periods. The blistering is proposed to occur from rupture of transalar connections through the failure of integrin-mediated adhesion processes during wing expansion. Of great interest, the DGs*-dependent blistering occurs even in the absence (null mutation) of protein kinase A, suggesting that DGs* utilizes either a cAMP-independent pathway or cAMP but not PKA. The first aim is to test the hypothesis that elevation of cAMP in wing epithelial cells is required for the generation of blistering. A system for monitoring intracellular cAMP levels based on expression of a beta-galactosidase reporter will be established, then cAMP will be modulated through overexpression of an adenylyl cyclase (rutabaga) or phosphodiesterase (dunce). The second aim will be to identify molecules which are components of the DGs*-activated pathway in wing epithelial cells. The investigator assumes that a subset of molecules mediating downstream effects exist at a critical level and will take advantage of the fact that most genes in Drosophila are dosage-compensated, in developing deficiency screens to identify genes which, when present in one copy, can suppress blister formation. The third aim is to test the idea that the function of the Gs pathway within wing epithelial cells is to regulate the adhesive properties of integrin molecules. Specific aspects of wing morphogenesis will be examined, as will the ability of genetic manipulations of genes encoding integrin proteins to enhance or suppress blister formation.
Effective start/end date9/30/978/31/02


  • National Institutes of Health: $225,777.00
  • National Institutes of Health: $239,234.00


  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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