Identification and characterization of a key planar cell polarity factor

描述（由申请人提供）：平面细胞极性（PCP）是上皮平面内细胞内的细胞极性，可以看到细胞的一侧与其他一侧不同。极化过程是高度组织化的，因为某些分子或结构只在细胞内的特定位置形成，从而产生定向极性。当PCP异常时，细胞极化要么变得随机，要么仍然有组织，但方向错误。许多组织和器官（心脏、肾脏、皮肤、心脏、大脑、脊髓、内耳等）需要正确的PCP才能正常形成。因此，PCP对这些器官的结构和功能至关重要。异常PCP可引起脑、脊髓、肾脏等疾病，并可能与其他器官疾病相关。最近，PCP也被发现与癌细胞转移过程中的迁移有关。PCP也存在于包括果蝇在内的所有动物中，在这些动物中研究PCP更容易、更有效。大多数PCP基因首先在果蝇中被发现，然后在老鼠、鱼、青蛙和人类中被发现。因此，果蝇是PCP研究的一个很好的模式生物。利用这种模式生物，我们发现了一个潜在的重要的PCP基因，它控制着PCP的方向。oatp30B-RNAi通过脱靶调控下调该基因的表达。我建议通过实验进一步鉴定该基因并剖析其控制PCP方向的功能。作为核心PCP基因，果蝇和人类的工作原理相似。因此，研究果蝇PCP的核心调控将对脊椎动物和人类PCP的研究产生广泛的影响，可能为儿童发育和人类健康提供重要的信息。

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.