The Genetics of Cell and Tissue Shape in Drosophila

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Jack 97-23791 The actin-myosin cytoskeleton controls the shape of cells in a variety of situations. Changes in the shapes of cells caused by contraction of the actin cytoskeleton are known to be responsible for tissue morphogenesis, invagination of epithelial sheets, cell rearrangement, and cell motility in a variety of organisms. Contraction of the actin cytoskeleton is caused by the action of nonmuscle myosin proteins on actin filaments. Preliminary results identify three mutations that prevent cells in various tissues--especially tubular epithelia and the nervous system--from assuming their proper shape. One of the three mutations, zipper, encodes nonmuscle myosin II. The products of the other two, raw and rib, are unknown. The rib and zip mutations are nearly identical in phenotype. Both cause embryonic defects and abnormalities in tissue morphology consistent with a function of their products in conferring cell shape. Mutations of raw cause a subset of the phenotypes of rib and zip mutants. In addition to the remarkable similarity of their phenotypes, mutations of the rib and zip genes are synthetically lethal, further suggesting that the products function in the same process. Experiments in this proposal are designed to test the hypothesis that the products of the raw and rib genes are required for the cell shape changes caused by the contraction of the actin cytoskeleton by nonmuscle myosin II. Tissues and cells of mutant embryos will be studied in greater detail to test the prediction that the abnormalities caused by the mutations will be consistent with defects in cell shape. In order to test hypotheses regarding the functional interaction between the raw and rib products and nonmuscle myosin, the distribution of filamentous actin and nonmuscle myosin between tissues and within cells will be compared in wild type and mutant animals. In addition, the requirement of other cytoskeletal components on tissue morphology will be examined by assessment of the mutant phenotypes and genetic i nteractions of mutations of the genes that encode them. Cloning of rib will be undertaken in order to characterize the sequence, cellular location, and biochemical interaction of its product with nonmuscle myosin II.