Analysis of the Wnt receptors Ror, Otk and Otk2 during nervous system development in Drosophila melanogaster

Abstract

Wnt signaling regulates many developmental and adult physiological processes. This is achieved through the activation of several distinct Wnt pathways. The outcome is determined by a specific combination of a Wnt ligand and one or several Wnt receptors. Ror receptor tyrosine kinases are Wnt receptors, which function in many developmental processes. So far, no phenotypic or functional data for the Drosophila Ror family member were available. Using a fly line expressing Ror-eGFP under the endogenous promoter, we could show that Drosophila Ror is expressed in the nervous system. The expression commences after germ band retraction and persists throughout embryonic development within the ventral nerve cord and the brain. It can also be observed in the sensory organs of the PNS. In the larval CNS it is visible in the membrane of all neuronal cells and in larval imaginal discs it can be observed in distinct cell clusters possibly representing proneuronal clusters. Embryos mutant for Ror display a mild CNS defect. A number of embryos in which the two PTK7 homologs (Otk and Otk2) were removed as well, display an even stronger CNS phenotype and increased larval lethality. Ror genetically interacts with Wnt5 and is able to bind to Wg, Wnt2, Wnt4, as well as to the receptors Fz, Fz2, Otk and Otk2. To identify downstream targets of Ror/Otk/Otk2-signaling, we performed a transcriptome analysis and compared differentially expressed genes in the respective single, double and triple mutants. We have identified various differentially expressed genes including several transcription factors and proteins involved in nervous system development. Future analyses of these will enable us to define the functions of Ror, Otk and Otk2 during Drosophila development.