GENETICS OF PROGRAMMED CELL-DEATH IN C-ELEGANS - PAST, PRESENT AND FUTURE

Genetic studies of the nematode Caenorhabditis elegans hale defined a variety of single-gene mutations that have specific effects on program med cell death. Analyses of the genes defined by these mutations have revealed that cell death is an active process that requires gene funct ion in cells that die. Specific genes are required not only to cause c ell death but also to protect cells from dying. Gene interaction studi es have defined a genetic pathway for the execution phase of programme d cell death in C, elegans. Molecular and biochemical findings are con sistent with the pathway proposed from these genetic studies and have also revealed that the protein products of certain cell-death genes in teract directly. This pathway appears to be conserved among organisms ns diverse as nematodes and humans. Important questions remain to be a nswered about programmed cell cell death in C elegans, For example, ho w does a cell decide to die? How is cell death initiated? What are the mechanisms of action of the cell-death protector and killer genes? Wh at genes lie downstream of the cell-death execution pathway? The conse rvation of the central cell-death pathway suggests that additional gen etic analyses of programmed cell death in C. elegans will help answer these questions, not only for this nematode but also for other organis ms, including ourselves.