Phagocytosis promotes programmed cell death in C-elegans

In the nematode Caenorhabditis elegans programmed cell death requires the k iller genes egl-1, ced-4 and ced-3 (refs 1 and 2), and the engulfment of dy ing cells requires the genes ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 (refs 3-5). Here we show that engulfment promotes programmed cell de ath. Mutations that cause partial loss of function of killer genes allow th e survival of some cells that are programmed to die, and mutations in engul fment genes enhance the frequency of this cell survival. Furthermore, mutat ions in engulfment genes alone allow the survival and differentiation of so me cells that would normally die. Engulfment genes probably act in engulfin g cells to promote death, as the expression in engulfing cells of ced-1, wh ich encodes a receptor that recognizes cell corpses(6), rescues the cell-ki lling defects of ced-1 mutants. We propose that engulfing cells act to ensu re that cells triggered to undergo programmed cell death by the CED-3 caspa se(7) die rather than recover after the initial stages of death.