Overexpression of Zeste White 3 Blocks Wingless Signaling in theDrosophilaEmbryonic Midgut

The extracellular signals encoded by the Wnt family of genes regulate growth and differentiation in several developmental processes in both vertebrates and invertebrates. Genetic studies of the signaling pathway of theDrosophilaWnt homologue, Wingless, have identified a number of genes, includingzeste white 3, which function to transduce the Wingless signal.zeste white 3encodes a serine/threonine kinase. We have previously proposed that the Wingless signal is mediated by repression of this kinase activity [E. Siegfried, E. L. Wilder, and N. Perrimon (1994)Nature367, 76–80]. Here we have tested this hypothesis by overexpressingzeste white 3in a tissue-specific fashion using the UAS/GAL4 binary expression system. We demonstrate that elevated levels ofzeste white 3in the ectoderm and mesoderm result in phenotypes that resemble a loss ofwingless. Overexpression ofzeste white 3in the mesoderm disrupts several Wingless-dependent processes including the specification of a unique cell type in the larval midgut, the formation of the second midgut constriction, and the expression of Wingless target genesUltrabithoraxanddecapentaplegicin the mesoderm andlabialin the endoderm. Zeste white 3 regulates the stability of Armadillo which is essential for transducing the Wingless signal to the nucleus. We show thatzeste white 3overexpression blocks Wingless signaling through the modulation of Armadillo since expression of a constitutively active form of Armadillo, which is independent of Zeste white 3 regulation, is epistatic to overexpression ofzeste white 3.