ECTOPIC E2F EXPRESSION INDUCES S-PHASE AND APOPTOSIS IN DROSOPHILA IMAGINAL DISCS

Previous experiments suggest that a key event in the commitment of cul tured mammalian cells to entering S phase is a rise in activity of the transcription factor E2F. In this report, we study the role of Drosop hila E2F in imaginal disc cells in vivo, by examining the distribution of the endogenous protein and studying the consequences of ectopic E2 F expression. First, we find that endogenous E2F falls from high to ve ry low levels as cells initiate DNA synthesis during a developmentally regulated G(1)-S-transition in the eye disc. Second, we find that ect opic E2F expression drives many otherwise quiescent cells to enter S p hase. Subsequently, cells throughout the discs express reaper (a regul ator of apoptosis) and then die. Third, we find that ectopic E2F expre ssion during S phase in normally cycling cells blocks their re-entry i nto S phase in the following cell cycle. Although we do not know the f ate of these cells, we suspect that ultimately they are killed by ecto pic E2F. Taken together, our results show that an elevation in the lev el of E2F is sufficient to induce imaginal disc cells to enter S phase . Furthermore, they suggest that the downregulation of E2F upon entry into S phase may be essential to prevent the induction of apoptosis.