Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans

Abstract

Genetic studies have identified over a dozen genes that function in programmed cell death (apoptosis) in the nematode Caenorhabditis elegans. Although the ultimate effects on cell survival or engulfment of mutations in each cell death gene have been extensively described, much less is known about how these mutations affect the kinetics of death and engulfment, or the interactions between these two processes. We have used four-dimensional-Nomarski time-lapse video microscopy to follow in detail how cell death genes regulate the extent and kinetics of apoptotic cell death and removal in the early C. elegans embryo. Here we show that blocking engulfment enhances cell survival when cells are subjected to weak pro-apoptotic signals. Thus, genes that mediate corpse removal can also function to actively kill cells.

Redundant cell death mechanisms as relics and backups

“…Thus, although caspase inhibition can successfully prevent the phenotypic manifestation of apoptosis, it often does not prevent cell death, which is likely to be executed through different mechanisms (including apoptosis-like cell death, autophagy and necrosis) 5,23,24,34,61 and perhaps through phagocytic recognition and destruction. 62,63 As mentioned above, it is possible that different cell types present in the same organism differ in their potential to execute cell death through distinct mechanisms. In this context, the tissue distribution of various effector mechanisms and of their redundancy may warrant a more detailed exploration, since it would determine the success of therapeutic approaches to control cell death.…”

Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

“…Activation of engulfment genes in the engulfing cell promotes apoptotic progression in injured cells. Clearance of apoptotic cells is carried out extremely rapidly in order to protect adjacent tissues from the release of harmful contents, which would promote inflammation and autoimmunity 56, 57, 58.…”

Cell death: what can we learn from flies? Editorial for the special review issue on Drosophila apoptosis

“…However, C-elegans studies show that engulfment genes take an active part in the activation of the apoptotic machinery. Hence, mutations in engulfment genes may enhance the survival of many cells normally destined to die [59,60]. A recent study in Drosophila went further by showing that during the cell competition process, engulfing genes such as draper (drpr), myoblast city (mbc) and Wiskott-Aldrich Syndrome (wasp) are required for the death of minutes cells (heterozygous mutants with a defective ribosomal protein) [61].…”