ABSTRACT
A small number of major regulatory (selector) genes have been identified in animals that control the development of particular organs or complex structures. In Drosophila, the vestigial gene is required for wing formation and is able to induce wing-like outgrowths on other structures. However, the molecular function of the nuclear Vestigial protein, which bears no informative similarities to other proteins, was unknown. Here, we show that Vestigial requires the function of the Scalloped protein, a member of the TEA family of transcriptional regulators, to directly activate the expression of genes involved in wing morphogenesis. Genetic and molecular analyses reveal that Vestigial regulates wing identity by forming a complex with the Scalloped protein that binds sequence specifically to essential sites in wing-specific enhancers. These enhancers also require the direct inputs of signaling pathways, and the response of an enhancer can be switched to another pathway through changes in signal-transducer binding sites. Combinatorial regulation by selector proteins and signal transducers is likely to be a general feature of the tissue-specific control of gene expression during organogenesis.
Subject(s)
Drosophila Proteins , Drosophila melanogaster/genetics , Gene Expression Regulation, Developmental , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Wings, Animal/embryology , Animals , Base Sequence , Binding Sites , Body Patterning/genetics , Cell Line , Cell Nucleus/metabolism , DNA Footprinting , DNA-Binding Proteins/genetics , DNA-Binding Proteins/isolation & purification , DNA-Binding Proteins/metabolism , Drosophila melanogaster/embryology , Enhancer Elements, Genetic/genetics , Genes, Insect , Models, Biological , Molecular Sequence Data , Nuclear Proteins/genetics , Recombinant Fusion Proteins/isolation & purification , Recombinant Fusion Proteins/metabolism , Sequence Deletion , Signal Transduction , TEA Domain Transcription Factors , Transcription Factors/genetics , Transcription Factors/isolation & purification , Wings, Animal/metabolismABSTRACT
The signal transduction pathway controlling determination of the identity of the R7 photoreceptor in the Drosophila eye is shown to harbor high levels of naturally occurring genetic variation. The number of ectopic R7 cells induced by the dosage-sensitive SevS11.1 transgene that encodes a mildly activated form of the Sevenless tyrosine kinase receptor is highly sensitive to the wild-type genetic background. Phenotypes range from complete suppression to massive overproduction of photoreceptors that exceeds reported effects of known single gene modifiers, and are to some extent sex-dependent. Signaling from the dominant gain-of-function Drosophila Epidermal Growth Factor Receptor (DER-Ellipse) mutations is also sensitive to the genetic backgrounds, but there is no correlation with the effects on SevS11.1. This implies that different genes and/or alleles modify the two activated receptor genotypes. The evolutionary significance of the existence of high levels of genetic variation in the absence of normal phenotypic variation is discussed.
