Dfrizzled-3, a new Drosophila Wnt receptor, acting as an attenuator of Wingless signaling in wingless hypomorphic mutants

In Drosophila, two Frizzled proteins, Frizzled and Dfrizzled-2, have been r eported to serve as receptors of Wingless. Here, we identified the third me mber of the 'Drosophila Frizzled family (Dfrizzled-3), In contrast to Dfriz zled-2, Dfrizzled-3 was transcriptionally upregulated by Wingless signaling . Although Dfrizzled-3 was capable of binding to Wingless in vitro, Wingles s-dependent Armadillo/beta-catenin stabilization occurred much less effecti vely in Drosophila cells transfected with Dfrizzled-3 than in those with Df rizzled-2, Flies lacking Dfrizzled-3 activity were viable and fertile, with few morphological defects. Genetic and immunochemical analysis indicated t hat the absence of Dfrizzled-3 activity suppresses the effects of hypomorph ic wingless mutations such as failure of wing and antenna formation and res tores target gene expression to the normal levels without change in wingles s expression. Wingless signaling may thus be attenuated by Dfrizzled-3 at l east in wingless hypomorphic mutants.