Specific interactions between vestigial and scalloped are required to promote wing tissue proliferation in Drosophila melanogaster

Abstract

The two genes vestigial (vg) and scalloped (sd) are required for wing development in Drosophila melanogaster. They present similar patterns of expression in second and third instar wing discs and similar wing mutant phenotypes. vg encodes a nuclear protein without any recognized nucleic acid-binding motif. Sd is a transcription factor homologous to the human TEF-1 factor whose promoter activity depends on cell-specific cofactors. We postulate that Vg could be a cofactor of Sd in the wing morphogenetic process and that, together, they could constitute a functional transcription complex. We investigated genetic interactions between the two genes. We show here that vg and sd co-operate in vivo in a manner dependent on the structure of the Vg protein. We ectopically expressed vg in the patch (ptc) domains. We show evidence that wing-like outgrowths induced by ectopic expression of vg are severely reduced in vg or sd mutant backgrounds. Accordingly, we demonstrate that ptc-GAL4-driven expression of vg induces both expressions of the endogenous vg and sd genes and that the two Vg and Sd proteins have to be produced together to promote wing proliferation. Furthermore, we show an interaction between the two proteins by double hybrid experiments in yeast. Our results therefore support the hypothesis that Sd and Vg directly interact in vivo to form a complex regulating the proliferation of wing tissue.

The Drosophila wing differentiation factor Vestigial–Scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc

“…Only sd ETX4 /Y males displayed an enhanced wing phenotype in a vg null / þ heterozygous background (Figure 4a, b). 11 Similarly, sd ETX4 /Y, dE2F 91 / þ males displayed a more severe mutant wing phenotype compared to sd ETX4 /Y males (Figure 4a, c), suggesting a genetic interaction between dE2F and sd.…”

“…Therefore, the complete loss of wing tissue in vg null homozygous mutant 7,11 and the impossibility to recover vg null clones 4,36 are probably due to both proliferation impairment and apoptosis triggering. The requirement for DHFR during both processes raises the possibility of mutual cross-talk between cell survival and proliferation that would rely on VG function and DNA synthesis.…”

“…11 The vg-GAL4 strain that drives GAL4 expression according to part of the vgBEenhancer was provided by M Hoffmann and S Morimura. The vgBE-lacZ strain that drives b-galactosidase expression according to the vgBE enhancer was described in Williams et al 8 The sd ETX4 strain is a sd-LacZ enhancer trap described in Campbell et al 13 The E2F rm729 line, which contains an enhancer trap inserted in the dE2F1 gene, is called E2F-lacZ in this study.…”

“…6,9 It has been shown that vg interacts genetically and molecularly with the scalloped (sd) gene product. [10][11][12] vg and sd are coexpressed in the wing imaginal disc and dimerization of VG and SD seems to be a prerequisite for translocation of the dimer to the nucleus, where it acts as a functional transcription factor. [12][13][14] In fact, in the heterodimer, SD contains the transcription enhancer activator (TEA) DNA binding domain, while VG provides the transcriptional activation domain.…”

“…10,12,14 It has been shown that ectopic expression of vg in other imaginal discs induces wing outgrowths, this being dependent on the presence of SD. 4,11 Therefore, vg seems to be required for both wing identity and cell proliferation, suggesting that the VG-SD dimer could be one of the links between signalling genes and genes involved in cell proliferation. 6 We have previously shown a strong interaction between specific antiproliferative drugs, such as methotrexate, aminopterin, fluorodeoxyuridine, and the phenotype of vg mutants.…”