ECTOPIC EXPRESSION OF DE2F AND DDP INDUCES CELL-PROLIFERATION AND DEATH IN THE DROSOPHILA EYE

The deregulation of E2F activity is thought to contribute to the uncon trolled proliferation of many tumor tells, While the effects of overex pressing E2F genes have been studied extensively in tissue culture, th e consequences of elevating E2F activity in vivo are unknown, To addre ss this issue, transgenic lines of Drosophila were studied in which ec topic expression of dE2F and dDP was targeted to the developing eye, T he co-expression of dDP or dE2F disrupted normal eye development, resu lting in abnormal patterns of bristles, cone cells and photoreceptors. dE2F/dDP expression caused ectopic S phases in post-mitotic cells of the eye imaginal disc but did not disrupt the onset of neuronal differ entiation. Most S phases were seen in uncommitted cells, although some cells that had initiated photoreceptor differentiation were also driv en into the cell cycle. Elevated expression of dE2F and dDP caused apo ptosis in the eve disc, The co-expression of baculo-virus p35 protein, an inhibitor of cell death, strongly enhanced the dE2F/dDP-dependent phenotype, These results show that, in this in vivo system, the elevat ion of E2F activity caused post-mitotic cells to enter the cell cycle, However, these cells failed to proliferate unless rescued from apopto sis.