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Abstract

Basement membranes (BMs) are sheet-like extracellular matrices that provide essential support to epithelial tissues. Epithelia are common drivers of morphogenesis, the process by which complex tissue shapes are generated during development. Recent evidence suggests that regulated changes in BM architecture can direct morphogenesis; however, the mechanisms by which cells remodel their associated BMs, and how BM structure influences tissue shape change, are largely unknown. The Drosophila egg chamber is an organ-like structure that transforms from a spherical to an ellipsoidal shape as it matures. This elongation coincides with two changes in the BM surrounding the egg chamber: an increase in levels of Type IV Collagen (Col IV), and the formation of a polarized network of linear fibrils. I have identified the mechanisms by which the egg chamber’s epithelial cells dynamically regulate the composition and structure of the BM, and elucidated the role of these remodeling events in egg chamber morphogenesis. I first identify the Collagen-binding protein SPARC as a negative regulator of egg chamber elongation, and show that SPARC down-regulation is necessary for the increase in Col IV levels to occur. I also observe a decrease in Perlecan levels during elongation, and show that Perlecan is a negative regulator of this process. Additionally, I identify a Rab10-mediated pathway by which newly synthesized BM proteins are secreted to the pericellular spaces between epithelial cells, where they assemble into fibrils and undergo oriented insertion into the BM by directed epithelial migration. By manipulating this pathway, I show that BM fibrils influence egg chamber morphogenesis. Finally, I describe unpublished work examining how and where polarized BM secretion occurs in the egg chamber. These data reveal that developing epithelia dynamically remodel their BMs, and that the properties of these matrices can provide crucial inputs to morphogenesis.

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