Regulation of epithelial barrier formation in Drosophila

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The ability to maintain an internal environment that is separated and distinct from the external environment is fundamental to the survival of all organisms. This function is performed in animals by epithelial tissues, which form or synthesize barriers that are essential for structural integrity, defense against infection, and internal homeostasis. In insects and other invertebrates, epithelia perform their barrier function in part by synthesizing extracellular structures such as the cuticle, eggshell, and peritrophic matrix: durable, cross-linked matrices composed of protein, chitin, lipid, and other small molecules. This award will support research into a novel genetic pathway that is critical to the formation of epithelial barriers in the fruit fly Drosophila melanogaster. The specific conservation of drd among insects strongly suggests that the results of the planned studies will be of broad interest to insect biologists and could be relevant in controlling insect-borne disease and developing novel insect control strategies.The gene drop-dead (drd) encodes an integral membrane protein and has traditionally been considered a neurodegeneration gene, due to the short adult lifespan and profound neurodegeneration displayed by drd mutant flies. However, data indicate a defect in the development of multiple epithelial barrier structures in drd mutants. The central hypothesis of this proposal is that drd is required for the formation or stabilization of extracellular epithelial barrier structures. The proposed experiments will use histologic, genetic, and biochemical approaches to characterize the pathways by which the drd gene product regulates barrier formation. Because insect barrier synthesis is not well understood and because drd was not previously recognized as essential to this process, these experiments will break new ground in our understanding of basic epithelial biology. The award will support training for 9 undergraduates, including at least three members of underrepresented minority (URM) groups recruited in collaboration with the Educational Opportunity Program at Marquette University. Research results will be disseminated through peer-reviewed publications and at regional or national scientific meetings. Any fly stocks that are of widespread interest will be donated to the Bloomington stock center (http://flystocks.bio.indiana.edu/) for maintenance and distribution.