In the nematode Caenorhabditis elegans programmed cell death requires the killer genes egl-1, ced-4 and ced-3 (refs 1 and 2), and the engulfment of dying cells requires the genes ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 (refs 3,4,5). Here we show that engulfment promotes programmed cell death. Mutations that cause partial loss of function of killer genes allow the survival of some cells that are programmed to die, and mutations in engulfment genes enhance the frequency of this cell survival. Furthermore, mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die. Engulfment genes probably act in engulfing cells to promote death, as the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses6, rescues the cell-killing defects of ced-1 mutants. We propose that engulfing cells act to ensure that cells triggered to undergo programmed cell death by the CED-3 caspase7 die rather than recover after the initial stages of death.
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We thank B. Galvin, B. Hersh and Z. Zhou for comments. P.W.R. was supported by a National Science Foundation Fellowship. S.C. was supported by a Howard Hughes Medical Institute (HHMI) postdoctoral fellowship, a Merck/MIT collaborative fellowship, and an NIH training grant. H.R.H. is an Investigator of the HHMI.
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Reddien, P., Cameron, S. & Horvitz, H. Phagocytosis promotes programmed cell death in C. elegans. Nature 412, 198–202 (2001). https://doi.org/10.1038/35084096
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