A Genetic Screen for Genes Involved in the FGF Signalling Pathway in Drosophila melanogaster

The FGF signal is important for cell survival, proliferation, differentiation and migration. It is not clear how the FGF signalling cascade is regulated. In order to identify genes downstream of FGF signalling, a gain-of-function (GOF) screen was conducted using the Drosophila compound eye as a model system. The screen was based on the observation that expression of an activated form of the FGF receptor and Dof together in the Drosophilia eye ('GMR>λ-fgfr, dof'), produces a rough eye phenotype, whereas expressing either alone has no effect. This implies that at least some of the components in the signalling cascade are present during Drosophila eye development. When one copy of raf, rhoA or rhoGEF was mutated, the rough eye phenotype of 'GMR>λ-fgfr, dof' flies was enhanced. In the screen, 'GMR>λ-fgfr, dof' flies were crossed to the EP collection and the progeny were screened for the modification of the rough eye phenotype. In total, 24 suppressors and 26 enhancers were obtained, which may affect 38 annotated genes. 8 lines did not have any interactions with other signalling pathways that I have tested, which are the PDGF and EGF signalling pathways, and pathways involving Cdc42 or Rac1. Nor were they found in any of the published GOF screens. In order to investigate the interaction of the candidates with the endogenous FGF signalling pathway, imprecise excisions of three candidates - EP719, EP3575 and EP863 - were generated and the mutant phenotypes were studied