Frizzled and DFrizzled-2 function as redundant receptors for Wingless during Drosophila embryonic development

In cell culture assays, Frizzled and Dfrizzled2, two members of the Frizzle d family of integral membrane proteins, are able to bind Wingless and trans duce the Wingless signal. To address the role of these proteins in the inta ct organism and to explore the question of specificity of ligand-receptor i nteractions in vivo, we have conducted a genetic analysis of frizzled and D frizzled2 in the embryo, These experiments utilize a small gamma-ray-induce d deficiency that uncovers Dfrizzled2. Mutants lacking maternal frizzled an d zygotic frizzled and Dfrizzled2 exhibit defects in the embryonic epidermi s, CNS, heart and midgut that are indistinguishable from those observed in wingless mutants. Epidermal patterning defects in the frizzled, Dfrizzled2 double-mutant embryos can be rescued by ectopic expression of either gene. In frizzled, Dfrizzled2 mutant embryos, ectopic production of Wingless does not detectably alter the epidermal patterning defect, but ectopic producti on of an activated form of Armadillo produces a naked cuticle phenotype ind istinguishable from that produced by ectopic production of activated Armadi llo in wild-type embryos, These experiments indicate that frizzled and Dfri zzled2 function downstream of wingless and upstream of armadillo, consisten t with their proposed roles as Wingless receptors, The lack of an effect on epidermal patterning of ectopic Wingless in a frizzled, Dfrizzled2 double mutant argues against the existence of additional Wingless receptors in the embryo or a model in which Frizzled and Dfrizzled2 act simply to present t he ligand to its bona fide receptor. These data lead to the conclusion that Frizzled and Dfrizzled2 function as redundant Wingless receptors in multip le embryonic tissues and that this role is accurately reflected in tissue c ulture experiments, The redundancy of Frizzled and Dfrizzled2 explains why Wingless receptors were not identified in earlier genetic screens for mutan ts defective in embryonic patterning.