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

• Antragsteller: Professor Dr. Andreas Wodarz
• Fachliche Zuordnung: Hämatologie, Onkologie
• Förderung: Förderung von 2007 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 45707573

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.

• DFG-Verfahren: Forschungsgruppen
• Teilprojekt zu: FOR 942: WNT signalling in development and tumor progression