Identification and characterization of a key planar cell polarity factor

关键平面细胞极性因子的识别和表征

• 批准号: 8679130
• 负责人: Jun Wu
• 金额: $ 8.48万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8679130
• 关键词: Abnormal Cell; Animal Model; Animals; Brain; Carrier Proteins; Cell Polarity; Cells; Child; Child Development; Cilia; Data; Development; Disease; Drosophila genus; Employee Strikes; Epithelial; Epithelium; Fatty acid glycerol esters; Fishes; Floor; Gene Expression; Gene Targeting; Genes; Genetic; Guidelines; Hair; Health; Heart; Human; Kidney; Kidney Diseases; Labyrinth; Location; Mammals; Mediating; Molecular; Morphogenesis; Mus; Neoplasm Metastasis; Neural tube; Organ; Organic Anion Transporters; Organism; Pathway interactions; Phenotype; Process; Proteins; RNA Interference; Rana; Randomized; Regulation; Role; Series; Side; Signal Transduction; Skin; Spinal Cord; Structure; Testing; Tissues; Vertebrates; Wing; Work; base; cancer cell; cell motility; human disease; insight; loss of function; mutant; public health relevance; research study; tool; transcriptome sequencing

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.

描述（由申请人提供）：平面细胞极性（PCP）是上皮平面中细胞内的细胞极性，可以观察到细胞的一侧与其他侧不同。 极化过程是高度组织化的，因为某些分子或结构仅在细胞内的特定位置形成，从而产生定向极性。 当PCP变得异常时，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，五氯苯酚对这些器官的结构和功能至关重要。 PCP异常可引起脑开放、脊髓开放和肾脏疾病等疾病，并可能与其他器官疾病有关。最近，PCP也被发现与转移过程中的癌细胞迁移有关。五氯苯酚也存在于包括果蝇在内的所有动物体内，对果蝇进行五氯苯酚研究比较容易，也比较有效。 大多数五氯苯酚基因首先在果蝇中发现，然后在小鼠、鱼类、青蛙和人类中发现。因此，果蝇是研究五氯苯酚的一种极好的模式生物。 利用这种模式生物，我们发现了一个潜在的重要的PCP基因，控制PCP的方向。oatp 30 B-RNAi通过脱靶调节下调该基因的表达。我建议实验，以进一步确定这个基因，并剖析其功能，控制PCP的方向。作为五氯苯酚的核心基因，果蝇和人类的作用相似。因此，研究果蝇体内五氯苯酚的核心调控机制将对脊椎动物和人类体内五氯苯酚的研究产生广泛影响，并可能为儿童发育和人类健康提供重要信息。