F-Actin Remodeling at Newly Forming Cell-Cell Junctions

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DESCRIPTION (provided by applicant): Epithelial cell sheets drive morphogenesis, and in adult tissues intact epithelia provide active barriers between tissue compartments. These functions require cells of the epithelia to be polarized and this polarity depends on the adhesion of cells-to-cells and cells-to-substrate. Loss of cell-cell adhesion precipitates several human disorders including, degenerative skin blistering diseases, cystic kidney diseases and cancer. In fact, diminished cell adhesion directly correlates with invasiveness of malignant cells; and invasiveness of carcinomas is countered by rescuing cell-cell adhesion. Given the necessity of cell-cell adhesion to the normal and pathological physiology of epithelia, knowing how cell-cell junctions are assembled and maintained is biologically and clinically significant. The Aims of this proposed work address the role played by actin in assembly/stability of cell-cell junctions in the primary epithelium of the Drosophila embryo. Specifically, the function of Nullo, a cell-cell junction protein that may coordinate membrane insertion with actin remodeling at junctions, will be studied using high-temporal and -spatial resolution confocal microscopy (3-dimensional and 4-dimensional). The goals of the work are 1) to characterize assembly/maintenance of cell-cell junctions with respect to actin dynamics in this model system, and 2) to demonstrate a cellular mechanism whereby membrane insertion at junctions orchestrates actin remodeling at junctions.