The Vestigial and Scalloped proteins act together to directly regulate wing-specific gene expression in Drosophila

A small number of major regulatory (selector) genes have been identified in animals that control the development of particular organs or complex struc tures. In Drosophila, the vestigial gene is required for wing formation and is able to induce wing-like outgrowths on other structures. However, the m olecular function of the nuclear Vestigial protein, which bears no informat ive similarities to other proteins, was unknown. Here, we show that Vestigi al requires the function of the Scalloped protein, a member of the TEA fami ly of transcriptional regulators, to directly activate the expression of ge nes involved in wing morphogenesis. Genetic and molecular analyses reveal t hat Vestigial regulates wing identity by forming a complex with the Scallop ed protein that binds sequence specifically to essential sites in wing-spec ific enhancers. These enhancers also require the direct inputs of signaling pathways, and the response of an enhancer can be switched to another pathw ay through changes in signal-transducer binding sites. Combinatorial regula tion by selector proteins and signal transducers is likely to be a general feature of the tissue-specific control of gene expression during organogene sis.