INTEGRATION OF ACTIN BEADED FILAMENT SYSTEM IN THE LENS

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The shape of the vertebrate lens is determined in part by a morphogenetic program in which dramatic changes in the actin and intermediate filament cytosekeletal network occur. An important component of this network is the lens fiber cell specific intermediate filaments, called the beaded filaments. The long-term objective of the research is to understand how the cytoskeletal components are integrated to accomplish the morphogenetic changes that occur during development and how these confer the lens' unique optical functions. The proposal seeks to determine: (1) how tropomodulin (Tmod), an actin filament capping protein that is upregulated during lens differentiation, actin and the beaded filaments are organized during development in the embryonic chick lens; (2) to determine biochemical and ultrastructural characteristics of the interactions between Tmod and actin and beaded filaments; (3) to elucidate the functional significance of the interactions between Tmod and these other cytoskeletal components. These goals will be accomplished using a combination of state of the art molecular, biochemical and microscopic techniques. The results of the work should provide a link between the biochemical characteristics of cytoskeletal assembly and lens morphology and have implications for the role of the cytoskeleton in lens fiber cell differentiation and cataract formation.