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The role of Gliotactin in planar cell polarity Venema, Dennis Roy

Abstract

Epithelial sheets exhibit apical-basal polarity and may also be polarized within the plane of the epithelium, a feature known as planar cell polarity, or PCP. In Drosophila, the pleated septate junction is a basolateral cell-cell junction that contributes to apicalbasal polarity. Gliotactin is a transmembrane protein with homology to serine esterases that localizes to the septate junction at the common vertex of three adjoining cells. Gliotactin is necessary for the function of the embryonic blood-nerve barrier which is formed by glial-glial septate junctions, as well as for septate junction formation in the embryonic epidermis. While septate junctions are a ubiquitous feature of epithelial sheets in Drosophila, the role of Gliotactin in post-embryonic tissues has not been addressed. In this thesis the role of Gliotactin in the development of polarized post-embyronic epithelia was investigated. The Drosophila wing epithelium has both apical-basal and planar polarity. Through mutant analysis it was demonstrated that Gliotactin is required for PCP in this epithelium. The Gliotactin wing PCP phenotype was sensitive to enhancement by the septate-junction mutants scribble, discs-large, coracle and Neurexin IV, and by the putative septate-junction mutant vulcan. Through genetic tests these mutations were found to function in the Gliotactin PCP pathway in epistasis groups consistent with previous work in the embyonic epidermis. Combinatorial septate-junction mutations were found to cause blisters at the wing margin, identifying a role for Gliotactin and other septate-junction components in adhesion between wing epithelial layers. The Gliotactin PCP pathway was shown to be independent of the frizzled PCP signaling pathway through cell biological and genetic assays. Finally, a novel component of the Gliotactin pathway was identified through a genetic screen for modifiers of Gliotactin PCP phenotypes. A model of Gliotactin function in/h'zz/ed-independent PCP in the wing is presented.

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