The overall goal of this project is to gain a detailed understanding ofthe molecular function of integrins a large family of cell surfacereceptors. Integrins are involved in many developmental processes andalso function in numerous fully differentiated cells. With respect toknown pathological conditions most studies of integrins have focused onthe circulatory system the immune system and the metastasis of tumorshowever it is likely that integrins will prove to be important inpathologies in other tissues and diseases as well.The PS integrins of Drosophila are very similar to vertebrate integrinsand provide a unique opportunity to examine integrin function in situ ina complex developmental system. We propose to: (1) Further define theinteraction of PS2 integrin with the fly matrix protein tiggrin usingour cell spreading assay and genetically engineered fragments of thetiggrin protein. Also begin steps to generate mutations in the tiggringene in order to undertake a genetic analysis of tiggrin function duringdevelopment. (2) Define the requirements for PS l integrin duringdevelopment using newly generated mutations in the mew gene whichencodes the alphaPS1 integrin subunit. This study will focus onComparisons between the myospheroid (betaPS) inflated (alphaPS2) and mewphenotypes and include analysis of genetic mosaics. (3) Continue togenerate and characterize hypomorphic mutations of myospheroid andcombine this with cell culture and phenotypic analyses to define domainsof integrins required for specific integrin functions. (4) Developmethods for the regulated expression of PS integrin transgenes in thedeveloping wing of Drosophila with the goal of using wing as a modelsystem for the fine dissection of integrin function during morphogenesisin situ. This phase of the project will include use of GAL4 enhancertrap technology as well as dissection of the regulatory regions ofintegrin genes in order to find enhancers that can provide the requiredpatterns of integrin transgene expression. (5) Use the transgenes in (4)in combination with the integrin mutants to dissect the detailedfunctions of integrins and integrin 'parts' during wing morphogenesis.This will involve the generation of clones of cells mutant for integrinfunction and attempts to rescue the mutant phenotypes by expression ofnormal and genetically altered integrin transgenes.