The long term goal is to examine the mechanisms through which integrins function during development. Drosophila is a model system for examining the functions of integrins since combined classical and molecular genetic techniques can be used to address the roles of integrins in a complex developing organism. The cellular molecules that associate with integrins, determine their genetic regulation and their potential roles in developmental signal transduction pathways will be identified and characterized. Experimentally, the functional significance of two highly conserved regions of the beta subunit of the Drosophila position specific integrin family, which is encoded by the lehthal(1)myospheroid (mys) gene will be determined. One region is derived from alternate splicing of mys and is thought to be in or near a region required for ligand binding and alpha/beta dimerization. Previous studies indicated that both alternate forms of the position specific integrin family contributed to embryonic development. The alternate forms of position specific integrin family may influence binding to particular ligands or alpha subunits during specific embryonic processes. The functional significance of the small and highly conserved cytoplasmic domain of the position specific integrin family is also addressed in this proposal. This region is associated with the cytoskeleton and intracellular communication. The experiments in this proposal will address the following questions: 1) Which embryonic processes require the position specific integrins? 2) Which of these processes can function normally with a particular form of the position specific integrin family? 3) Where are the alternative mRNAs of mys and the alternative forms of the integrins found in the developing embryo? 4) Do particular forms of the position specific integrin family influence cell spreading on specific matrix molecules and influence dimerization with alpha subunits? 5) Which regions of the cy toplasmic domain of the integrins affect developmental processes? 6) What are the molecules that associate with the position specific integrins? These questions will be answered using molecular, genetic and cellular techniques.
