The integrin superfamily of cell surface receptors includes may of the receptors for extracellular matrix components. Integrins have been implicated in many morphogenetic and differentiative events during embryogenesis, and a better understanding of integrin function will be crucial to understanding basic developmental processes, and therefore certain congenital defects, in humans. This proposal outlines a combined genetic, cellular and molecular biological approach to basic questions of integrin structure-function relationships. Using the PS integrins of Drosophila as our model system, the following lines of research will be pursued: 1. Mutations will be generated in the genes coding for the alpha and beta chains of the integrins. 2. The functions and protein associations of the integrins will be studied in situ, using clonal analysis, conditional alleles, and other genetic approaches. 3. A cell transformation system (in which integrin genes are introduced into and expressed in a cultured cell line) will be developed; this system will permit cell biological assays for specific integrin functions. 4. The functions of mutant integrins will be examined in the transformed cell lines, and the molecular bases of the mutations will be examined in the transformed cell lines, and the molecular bases of the mutations will be determined by sequencing. 5. The transformation system will be used in combination with in vitro mutagenesis to produce integrins with specific functional defects. These mutants can then be introduced into whole files, where their developmental consequences can be determined.
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