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Wnt genes belong to a multigene family encoding secreted proteins that activate receptor-mediated signal transduction pathways involved in both development and disease. The best-understood Wnt pathway is called the Wnt/?-catenin pathway, because the Wnt signal leads to activation of the nuclear functions of ?-catenin, which in turn activates gene expression leading to cell survival, proliferation, or differentiation. A second vertebrate Wnt pathway, the Wnt/Ca2+ pathway, promotes intracellular Ca2+ release and regulates cell movements in development and in some cancers. We had three major goals in studying Wnts. Our first goal was to understand the normal functions of Wnt pathways in vertebrates. Our second goal was to understand the biochemistry of a Wnt signal. Our third goal was to leverage this understanding of the normal biology of Wnts to determine whether Wnt signaling is involved in various diseases and, if it is, to make contributions to developing therapies.