The Wnt family of proto-oncogenes encodes secreted signaling proteins that are required for mouse development. The Drosophila Wnt homolog, the wingless (Wg) segment polarity gene, mediates a signal transduction pathway in which the downstream elements appear to be conserved through evolution. One such element, the dishevelled gene product, becomes hyperphosphorylated and translocates to the plasma membrane in response to Wg (Yanagawa et al., 1995). We report here that the mouse Dishevelled-1 (Dvl-1) and Dishevelled-2 genes encode proteins that are differentially localized in Wnt-overexpressing PC12 cell lines (PC12/Wnt). Whereas Dvl-1 and Dvl-2 proteins are limited to the soluble fraction of parental PC12 cells, PC12/Wnt cells display a subset of Dvl-1 protein associated with the membrane and Dvl-2 protein with the cytoskeletal fraction. These results suggest a conserved role for Dvl in Wnt/wg signal transduction.