Role Playing, H. Robert Horvitz, John Sulston
Cell fate and cell death are central to any multicellular organism’s normal development. Our lab pioneered the use of the nematode Caenorhabditis elegans in studying the fundamental processes that control cell fate and death, two events that cannot be divorced from one another. We discovered several cell lineage mutants, including lin-4, let-7, lin-12 and lin-14, which affect developmental timing and control. The effects of some of these mutations on the development of the vulva are examined here, which includes programmed cell death (PCD). The molecular genetic pathway of PCD was determined over the course of more than 20 years of study. The following mutations are known to act in PCD; ces-2, ces-1, tra-1, egl-1, ced-9, ced-3, ced-4, ced-11, ced-1, ced-6, ced-7, ced-2, ced-5, ced-10, ced-12 and nuc-1. The discovery of human homologues of most of these genes has shown that the PCD pathways in worms and humans are evolutionarily conserved. This conservation has proved to have immense implications on research for cures of many human disorders like neurodegenerative diseases and cancer, which are hypothesized to be caused by malfunctions in the PCD pathway. C. elegans has proved to be a truly noble organism, providing targets in the PCD pathway for intervention aimed at developing potential therapies.
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