Bves Function in Corneal Development and Regeneration

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DESCRIPTION (provided by applicant): Cell adhesion and movement play critical roles in the developing and adult cornea as well as in corneal regeneration. In all these processes, cell adhesion molecules regulate epithelial growth, movement, and stability. We have discovered a new cell adhesion molecule (Bves) that is expressed in specific cell populations of the developing and adult eye, including the corneal epithelium. Importantly, our preliminary data show: 1) Bves is one of the first adhesion molecules that traffics to points of cell/cell contact in developing and regenerating epithelia and 2) that disruption of Byes function inhibits epithelial formation and outgrowth. These emerging data lead to our central hypothesis that Bves plays an important role in the growth, maintenance and regeneration of corneal epithelium. To test this hypothesis, we propose the following specific aims: 1. To determine the precise temporal and spatial expression patterns of Bves during corneal development; 2. To determine the function of Bves during corneal development and; 3. To determine the function of Bves in the fully developed corneal epithelium. In vitro models of human corneal wounding will be used to determine cellular function of Bves in repair. While cell movement during development, renewal and regeneration is critical to corneal function, the underlying molecular mechanisms governing these processes are not known. As Bves is a regulator of cell adhesion and epithelial morphogenesis, elucidating its role in corneal development and homeostasis is an important step in understanding corneal biology. Our proposed studies will determine the role of Bves in the cornea and, in a larger sense, the cellular and molecular regulation of morphogenesis and wound healing in the eye.