Patterning within a Neuroepithelium

Icahn School Of Medicine At Mount Sinai, New York NY

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Abstract

DESCRIPTION (provided by applicant): Patterning is a fundamental process that allows tissues to develop complexity through the use of relatively simple 'rules'. To explore these rules and understand how epithelia assemble into useful tissues, my laboratory has focused on the developing Drosophila pupil eye. The fly eye is a relatively simple neuroepithelium composed of several hundred 'ommatidia' (visual units) precisely arranged in a hexagonal array across the eye field. This precise pattern is required to re-create a coherent visual field. Patterning of the ommatidial array is achieved by precise arrangement of interommatidial precursor cells. These IPCs are glial-like support cells; movement within the epithelium coupled with selective cell death re-arranges them into an interweaving hexagonal lattice. This process requires several surface factors including Drosophila orthologs of heterophilic adhesion molecules of the Nephrin super family and E-Cadherin. Notch, Wingless, and Dpp pathways provide local signaling. In this proposal, we extend our understanding of these surface events to the Drosophila EGF-Receptor. Further, we connect surface events to intracellular signaling, which in turn leads to dynamic remodeling of the Actin cytoskeleton. Pathways include the fly CD2AP/CIN85 ortholog Cindr and the ZO-1 ortholog Pyd. We extend this work to include new regulators of the Actin cytoskeleton, with an emphasis on their ability to mediate the dynamic cytoskeletal re-arrangements necessary for a cell to respond to extracellular signals and move into its correct niche.