Regulation of planar cell polarity and epithelial remodeling by the fat cadherin.

摘要

Epithelial tissues exhibit a diverse range of morphologies that support specific functions within the body. During morphogenesis, cells within a tissue must coordinately receive and respond to spatial information; this ability is reflected by the polarization of molecules, structures, or behaviors within the plane of the tissue, a property known as planar cell polarity. This dissertation describes the morphogenesis of denticle-producing cells in the Drosophila embryo, which display a planar polarized organization of the actin-based denticle structure, adherens junctions, and the microtubule cytoskeleton. Denticle-producing cells undergo changes in morphology accompanied by polarized remodeling of cellular junctions. Fat, an evolutionarily conserved cadherin, was required for all of these aspects of planar polarized cell organization and behavior, suggesting that Fat signaling provides a common spatial cue that influences diverse classes of cell biological processes involving the cytoskeleton, adhesion, and contractility. Polarized structures were readily visible using fixed and live imaging of intact embryos, and I present quantitative methods for describing the behavior of these structures over time. My findings additionally implicate the myosin Dachs, Hippo/Warts signaling, and Notch activity as mechanisms that influence planar polarity in the embryo. The work presented in this dissertation demonstrates the tractability of denticle-producing cells as a model system for studying planar cell polarity, and has identified the Fat cadherin as a molecular starting point from which to investigate diverse mechanisms of epithelial morphogenesis.