WNT GENES AND SIGNALING IN XENOPUS

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Wnts are secreted ligands which activate receptor-mediated signaling pathways. Vertebrate Wnts and their signaling pathways have been implicated in playing key roles in axis specification, in patterning mesoderm and the nervous system, in providing polarity to limbs, and in organogenesis. When inappropriately activated, components of the Wnt pathways may be linked to various human cancers notably colorectal cancer and melanoma. The current proposal represents a competing continuation application, to maintain funding for our work on Wnt genes and their signaling pathways in Xenopus. As the previous specific aims have largely been answered, our present proposal introduces new specific aims to address recent questions arising from this prior support. Whereas many of the previous specific aims asked embryological questions, the current focus is on Wnt signal transduction. Aim 1 uses yeast-two hybrid screens, and mass spectroscopy analysis, to identify new components of the Wnt-1/Frizzled-1 pathway. Aim 2 investigates the biochemistry of the distinct Wnt-5a/Frizzled-2 pathway which we discovered in the prior two project periods. Aim 3 investigates the target genes of Wnt signaling and their functions in development. Given the high degree of conservation of the Wnt-1 signaling pathway in evolution, it is likely the results of this work in Xenopus will continue to directly apply to Wnt signaling in other vertebrates.