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）是在大多数（如果不是全部的话）高等动物中发现的一种现象，在这种现象中，细胞的方向或形成组织的细胞中亚细胞结构的定位与邻近细胞协调。例如，苍蝇翅膀上的毛都指向同一个方向，老鼠背上的毛或肺呼吸上皮上的纤毛也是如此。PCP是由一组进化上保守的基因控制的，大多数（但不是所有）在脊椎动物中起作用的PCP基因在果蝇中也有相关的功能。脊椎动物PTK7基因是一个例外，它编码一种催化活性不强的酪氨酸激酶受体，是控制青蛙和老鼠PCP所必需的。据报道，果蝇PTK7同源基因的突变，即基因脱轨（otk），不会引起果蝇PCP表型。我们发现，与之前的报道相反，完全敲除otk的纯合子果蝇是可存活和可生育的，并且确实没有显示PCP表型。然而，我们发现了第二个密切相关的基因（CG8964），紧邻otk，可能在PCP中与otk一起冗余发挥作用，也可能在Wnt信号传导中发挥作用。在这个项目中，我们的目标是研究PCP和Wnt信号的单敲除和双敲除果蝇。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，我们期望在PTK7在PCP和Wnt信号传导中的作用机制方面获得重大的知识。

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.