ARGOS INDUCES PROGRAMMED CELL-DEATH IN THE DEVELOPING DROSOPHILA EYE BY INHIBITION OF THE RAS PATHWAY

We studied the role of Has signaling in the regulation of cell death d uring Drosophila eye development. Overexpression of Argos, a diffusibl e inhibitor of the EGF receptor and pas signaling, caused excessive ce ll death in developing eyes at pupal stages. The Argos-induced cell de ath was suppressed by coexpression of the anti-apoptotic genes p35, di ap1, or diap2 in the eye as well as by the Df(3L)H99 chromosomal delet ion that lacks three apoptosis-inducing genes, reaper, head involution defective(hid) and grim. Transient misexpression of the activated Ras 1 protein (Ras1(V12)) later in pupal development suppressed the Argos- induced cell death. Thus, Argos-induced cell death seemed to have resu lted from the suppression of the anti-apoptotic function of Has. Conve rsely, cell death induced by overexpression of Hid was suppressed by g ain-of-function mutations of the genes coding for MEK and ERK. These r esults support the idea that Has signaling functions in two distinct p rocesses during eye development, first triggering the recruitment of c ells and later negatively regulating cell death.