The role of Ena/VASP proteins in muscle development

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DESCRIPTION (provided by applicant): The role of Ena/VASP proteins in the organization of the actin cytoskeleton and the regulation of cell motility and axon outgrowth has been well established. However, their expression in embryonic muscle and muscle precursors suggests an additional role in the organization and differentiation of muscles during development. I propose to examine the spatial and temporal expression, and the subcellular localization of Ena/VASP proteins during muscle development, using both Xenopus embryos and cultured primary chick skeletal muscle cells. Construction and expression of deletion mutants of these proteins will allow determination of the domains necessary for targeting to specific subcellular Iocalizations, and provide insights into the molecular basis of Ena/VASP function in the myotome. Using a dominant negative construct and morpholino oligonucleotides to specifically inhibit Ena/VASP protein function and expression, I will investigate the effects of this loss on cytoskeletal and cellular structure and function during development. These investigations will elucidate the role of Ena/VASP proteins in skeletal muscle development, and may produce novel information concerning the molecular and cellular basis of muscle adaptation and disease.