Overexpression of zeste white 3 blocks wingless signaling in the Drosophila embryonic 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 the Drosophila Wnt homologue, Wingless, have identified a number of genes, including zeste white 3, which function to transduce the Wingless signal. zeste white 3 encodes 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) Nature 367, 76-80]. Here we have tested this hypothesis by overexpressing zeste white 3 in a tissue-specific fashion using the UAS/GAL4 binary expression system. We demonstrate that elevated levels of zeste white 3 in the ectoderm and mesoderm result in phenotypes that resemble a loss of wingless. Overexpression of zeste white 3 in 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 genes Ultrabithorax and decapentaplegic in the mesoderm and labial in the endoderm. Zeste white 3 regulates the stability of Armadillo which is essential for transducing the Wingless signal to the nucleus. We show that zeste white 3 overexpression 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 of zeste white 3.