Characterizing Novel Wnt Signaling Pathway Components

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DESCRIPTION (provided by applicant): Canonical Wnt signaling regulates embryonic development and cell fate and proliferation decisions in all vertebrates. There is also a non-canonical signaling pathway that regulates planar cell polarity (PCP). Mutations in several of the proteins acting in these signaling pathways are associated with numerous epithelial cancers. Preliminary work indicates that a novel Drosophila G-protein coupled receptor (GPCR) could have a role in Wnt signaling. We have also identified a genomic lesion resulting in a phenotype reassembling wingless. We propose that this GPCR and this unidentified gene represent novel Wnt signaling factors and we will determine their specific roles using genetic and biochemical techniques. We will map the genomic lesion and then define its role in the Wnt pathway by generating a null allele and measuring its effect on downstream signaling events. We will determine the phenotype of a GPCR knock out using immunofluorescence and cell biological studies. We will then use genetics to place this novel gene in the Wnt pathway. Similar cell biological and genetic experiments will then be done to determine the GPCR's role in PCP signaling.