Identification and characterization of a key planar cell polarity factor

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DESCRIPTION (provided by applicant): Planar cell polarity (PCP) is the cell polarity within a cell in the plane of the epithelium that can be visualized as one side of the cell is different fro other sides. The polarization process is highly organized as certain molecules or structures only form at specific locations within the cell creating a directional polarity. When PCP becomes abnormal, cell polarization either becomes random or is still organized but in the wrong direction. Many tissues and organs (heart, kidney, skin, heart, brain, spinal cord, inner ear, etc) require correct PCP to form properly. Therefore, PCP is essential for the structures and functions of these organs. Abnormal PCP could cause diseases such as open brain, open spinal cord and kidney diseases, and be potentially related to diseases of other organs. Recently, PCP is also discovered to be associated to cancer cell migration during the metastasis. PCP also exists in all animals including the fruit fly, where studying PCP is easier and more efficient. Most PCP genes were first identified in the fruit fly, then found in mouse, fish, frog and human. Therefore, the fruit fly is an excellent model organism for PCP studies. Using this model organism, we found a potentially important PCP gene that controls the PCP direction. The expression of this gene is down-regulated by oatp30B-RNAi through off-target regulation. I propose experiments to further identify this gene and dissect its functions in controlling PCP direction. As core PCP genes work similarly in fruit fly as in human. Therefore, studying core PCP regulation in the fruit fly will have broad influence on PCP studies in vertebrate animals and human, potentially providing important information related to child development and human health.