Steitz M C, Wickenheisser J K, Siegfried E
Department of Biology and Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802, USA.
Dev Biol. 1998 May 15;197(2):218-33. doi: 10.1006/dbio.1998.8884.
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.
Wnt基因家族编码的细胞外信号在脊椎动物和无脊椎动物的多个发育过程中调节生长和分化。对果蝇Wnt同源物无翅（Wingless）信号通路的遗传学研究已经鉴定出许多基因，包括小体白色3（zeste white 3），其功能是转导无翅信号。小体白色3编码一种丝氨酸/苏氨酸激酶。我们之前曾提出，无翅信号是通过抑制这种激酶活性来介导的[E. 西格弗里德、E.L. 怀尔德和N. 佩里蒙（1994年）《自然》367卷，76 - 80页]。在此，我们使用UAS/GAL4二元表达系统以组织特异性方式过表达小体白色3来检验这一假说。我们证明，外胚层和中胚层中小体白色3水平的升高会导致类似于无翅缺失的表型。在中胚层中过表达小体白色3会破坏几个依赖无翅的过程，包括幼虫中肠中一种独特细胞类型的特化、第二个中肠收缩的形成，以及中胚层中无翅靶基因超双胸（Ultrabithorax）和脱壳蛋白（decapentaplegic）以及内胚层中唇（labial）的表达。小体白色3调节犰狳（Armadillo）的稳定性，而犰狳对于将无翅信号转导至细胞核至关重要。我们表明小体白色3的过表达通过调节犰狳来阻断无翅信号，因为一种组成型活性形式的犰狳的表达独立于小体白色3的调节，对小体白色3的过表达具有上位性。
