GROWTH CONTROL IN THE DROSOPHILA WING

Fred Hutchinson Cancer Research Center, Seattle WA

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Abstract

The Drosophila wing develops from an epithelial primordium - an imaginal disc - that grows from 38 to approximately 50,000 cells in a 4-day period. Growth and pattern formation occur coincidentally during this period, and are controlled by a set of conserved cell signaling molecules including wingless (WG), decapentaplegic (DPP), and the EGFR ligand Vein (VN). Each of these signals is essential for wing patterning and is also required for normal cell proliferation. Inappropriate activation of each signaling pathway causes repatterned Outgrowths, whereas loss of each causes severe reductions in growth. The genes that regulate cell cycle progression in response to these signals are also highly conserved and include the S-phase initiator Cyclin E the M-phase initiator String (Cdc25), and the transcriptional regulators E2F and RBF (a retinoblastoma homolog). We propose to test how signaling regulates cell proliferation in the developing wing via three complementary approaches. First, we will work upstream from the limiting cell cycle regulators string and E2F, to determine how their expression and activity are controlled in vivo in the wing. Second, we will work downstream from WG, DPP, and VN to characterize how they regulate growth and cell cycle progression. Third, we will perform genetic screens to identify cell autonomous growth regulators, which we be believe may link signaling to cell cycle controls. Wing development in Drosophila bears striking similarities to vertebrate limb and organ development, both morphogenetically and molecularly. Thus we expect this work to be highly relevant to growth control in human development, tissue homeostasis, wound healing, and regeneration.