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.This proposal is to create a Center for Wnt/Wingless Signaling (CWGS) to investigate Wnt/Wingless signaling in the model organism, Caenorhabditis elegans. Even though C. elegans lacks a typical Wnt gene family, the key Wnt/Wingless signaling pathways are conserved. C. elegans Wnt and Wnt-like genes have been identified and many have been shown to be important for development and cellular function. This laboratory previously showed that Wnt signaling is required for the formation of the vulval precursor cells (VPCs) and the basolateral membranes of the epithelial cells that comprise the vulva. The VPCs develop from the hyp7 to hyp11 primordial germline cells, and these cells are the source of a single Wnt family member, Wnt-1, which is required for proper VPC formation. The loss of other Wnt genes leads to more extreme phenotypes and suggests that they are redundant in this process. Based on this work, the overall goal of this Center is to identify novel genes in the Wnt signaling pathways and determine how they work together and with Wnt-1 to control VPC formation. This Center will be led by the PI, a molecular and cell biologist, and will have two co-PI's, a C. elegans biologist and a developmental biologist. The resulting Center will have interactions with other investigators to develop new technologies as well as new experimental models that will facilitate discovery. The goal of the research is to define the novel genes in the Wnt pathways, how they work together to control VPC formation, and how they interact with Wnt-1. The specific aims are to: 1. Identify new Wnt family members, 2. Test the function of the newly identified genes in the Wnt pathway, and 3. Define the mechanisms of Wnt-1 activity.
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