Genetic dissection of Myc function in Drosophila. P. Gallant 1, C. Li 1, L. Montero 1, L.A. Johnston 2, R.N. Eisenman 3. 1) University of Zurich, Zoological Institute, Winterthurerstrasse 190, 8057 Zurich, Switzerland; 2) Columbia University, Dept. of Genetics & Development, 701 West 168th St, New York, NY10032; 3) Fred Hutchinson Cancer Research Center, Division of Basic Sciences, 1100 Fairview Ave N, Seattle WA98109-1024.
The Myc/Max/Mad network of transcription factors is involved in cell proliferation, apoptosis, differentiation, and neoplasia in vertebrates, but the physiological roles of these proteins, and the pathways through which they act are only beginning to be understood. In order to address these issues in a genetically tractable model organism, we are studying the Drosophila homolog of Myc, Dmyc. Overexpression of Myc in flies induces a massive increase in cell size and accelerates passage through G1 phase of the cell cycle. Conversely, hypomorphic dmyc mutations show a number of recessive traits (including small body and bristle size, a delay in development, and clonal competition) that are characteristic for mutations defective in growth. These results suggest the control of protein synthesis and cellular growth as a primary function of Myc. To identify novel genes acting downstream of Myc in the control of growth we have initiated a genetic screen. High level ectopic expression of Dmyc in the developing eyes results in aberrant adult eye morphology. This phenotype has been used in a search for dominant modifiers of Dmyc function. We have generated 3200 independent (EP) transposon insertion lines and found 54 of them to act as dominant modifiers of the Dmyc-phenotype. Their molecular and genetic characterisation is currently ongoing.