Functional analysis of off track and CG8964, the Drosophila homologs of the vertebrate planar cell polarity gene PTK7

脊椎动物平面细胞极性基因PTK7的果蝇同源物off track和CG8964的功能分析

• 批准号: 52875558
• 负责人: Professor Dr. Andreas Wodarz
• 金额: --
• 依托单位: Institut I für Anatomie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/52875558?language=en
• 关键词: Functional; analysis; off; track; CG8964

Planar cell polarity (PCP) is a phenomenon found in most, if not all, higher animals, in which the orientation of cells or the positioning of subcellular structures in cells that form a tissue is coordinated with the neighboring cells. For instance, the hairs on the wing of a fly all point in the same direction, and so do the hairs on the back of a mouse or the cilia in the respiratory epithelium of the lung. PCP is controlled by an evolutionarily conserved group of genes and most, but not all PCP genes with a function in vertebrates also have a related function in the fruit fly Drosophila. One exception is the vertebrate PTK7 gene, which encodes a catalytically inactive receptor tyrosine kinase and is required for the control of PCP in frogs and mice. Mutation of a Drosophila homolog of PTK7, the gene off track (otk), was reported not to cause PCP phenotypes in the fly. We found that in contrast to previous reports, flies homozygous for a complete knock-out of otk are viable and fertile and indeed do not show PCP phenotypes. However, we discovered a second closely related gene (CG8964) immediately adjacent to otk that could function redundantly with otk in PCP and potentially also in Wnt signaling. In this project we aim to study single and double knock-out flies for both genes with respect to PCP and Wnt signaling. Since the Drosophila system is much better suited for cell biological analyses, including high-resolution light microscopy and genetic interaction studies than the frog or the mouse, we expect a significant gain of knowledge on the mechanism of PTK7 function in PCP and Wnt signaling.

平面细胞极性（PCP）是在大多数高等动物中发现的一种现象，其中细胞的取向或形成组织的细胞中亚细胞结构的定位与相邻细胞相协调。例如，苍蝇翅膀上的毛发都指向同一个方向，老鼠背部的毛发或肺部呼吸上皮的纤毛也是如此。五氯苯酚受一组进化上保守的基因控制，在脊椎动物中具有功能的大多数五氯苯酚基因在果蝇中也具有相关功能。一个例外是脊椎动物的PTK7基因，该基因编码一种无催化活性的受体酪氨酸激酶，是控制青蛙和小鼠体内五氯苯酚所必需的。据报道，PTK7基因（otk基因）的果蝇同源物突变不会导致果蝇出现PCP表型。我们发现，与以前的报告相反，苍蝇纯合子的otk基因完全敲除是可行的和肥沃的，确实不显示PCP表型。然而，我们发现了第二个密切相关的基因（CG8964）直接相邻的otk，可以冗余地与otk在PCP和潜在的Wnt信号转导。在这个项目中，我们的目标是研究单和双敲除苍蝇的两个基因方面的PCP和Wnt信号。由于果蝇系统比青蛙或小鼠更适合于细胞生物学分析，包括高分辨率光学显微镜和遗传相互作用研究，因此我们期望对PCP和Wnt信号转导中PTK7功能机制的知识有显着的收获。