The molecular mechanism of programmed cell death in C. elegans.

Programmed cell death or apoptosis plays a fundamental role during animal development, metamorphosis, and tissue homeostasis. It is a genetically controlled physiological process that comprises two distinct and sequential processes: the death of cells, and their subsequent removal by engulfing cells. In the nematode C. elegans, genetic studies led to the discovery of 15 genes that function in programmed cell death (FIG. 1). These 15 genes have been divided into four groups based on the order of their activity during the process of programmed cell death: (1) those involved in the decision making (ces-1 and ces-2); (2) in the process of execution (ced-3, ced-4, ced-9 and egl-1); (3) in the engulfment of dying cells by engulfing cells (ced-1, ced-2, ced-5, ced-6, ced-7, ced-10, ced-12); and (4) those in the degradation of cell corpses within engulfing cells (nuc-1). In the last five years, several genes in the genetic pathway of programmed cell death have been shown to be conserved across a wide range of species; all genes involved in the step of execution in C. elegans have their corresponding mammalian homologs (FIG. 2). Furthermore, emerging evidence from molecular studies of engulfment genes in several species suggests that the signaling process from apoptotic cells to engulfing cells and the subsequent engulfment process might be also conserved across species (TABLE 1).