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

平面细胞极性(PCP)是一种在大多数(如果不是全部)高等动物中发现的现象，在这种现象中，形成组织的细胞的方向或亚细胞结构的位置与邻近细胞协调。例如，苍蝇翅膀上的毛发都指向同一个方向，小鼠背部的毛发或肺部呼吸道上皮中的纤毛也是如此。PCP是由进化上保守的一组基因控制的，在脊椎动物中具有功能的大部分但不是所有的PCP基因在果蝇中也有相关的功能。一个例外是脊椎动物的PTK7基因，它编码一种催化失活的受体酪氨酸激酶，是青蛙和小鼠控制PCP所必需的。据报道，果蝇PTK7的同源基因脱轨(OTK)的突变不会导致果蝇的PCP表型。我们发现，与之前的报告相反，完全敲除OTK的纯合果蝇是存活和可生育的，确实不显示PCP表型。然而，我们发现了与OTK相邻的第二个密切相关的基因(CG8964)，该基因可以在PCP中与OTK冗余地发挥作用，并可能也在Wnt信号中发挥作用。在这个项目中，我们的目标是研究与PCP和Wnt信号有关的单基因和双基因敲除果蝇。由于果蝇系统比青蛙或小鼠更适合细胞生物学分析，包括高分辨率光学显微镜和遗传相互作用研究，我们预计PTK7在PCP和Wnt信号转导中的作用机制方面的知识将获得重大进展。

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.