摘要：

The nematode Caenorhabditis elegans seems so well suited to investigation of genetically specified cell death that one might also suspect that it was designed for this purpose. The complete cell lineage of this nematode has been recorded. Thus, it is well established that of 1090 somatic cells generated during hermaphrodite development, 131 identified cells undergo programmed cell death (PCD) at characteristic times. Because the cuticle of the animal is transparent and individual cells are easily identified, cell deaths can be observed while they occur in the living animal. The ease of observation of specific cells, coupled with the fact that C. elegans is readily amenable to genetic analysis, has allowed mutations to be identified that either disrupt the normal pattern of PCD or cause inappropriate cell death. Molecular analysis of the identified genes is facilitated by the fact that the genetic map has been aligned with the physical map of the C. elegans genome so each chromosome is now nearly completely represented by an overlapping collection of cosmid or YAC clones that include defined genetic loci. In addition, significant progress toward sequencing the genome has been accomplished. Finally, it is possible to construct transgenic animals so the activities of engineered genes can be assayed in vivo. Two types of cell death have been studied in C. elegans. One type is PCD, which occurs as a component of normal development. Genetic studies have led to the elaboration of a genetic pathway for PCD that includes a negative regulator, ced-9 (cell death abnormal), that acts to prevent PCD and two genes, ced-3 and ced-4, that are involved in the execution of the death program. A third group of genes (ced-1, ced-2, ced-5, ced-5, ced-7, ced-8, ced-10) is required for efficient removal of corpses of dead cells. Cells undergoing PCD exhibit stereotypic morphological changes. A second type of cell death studied in C. elegans resembles necrosis and is characterized by swelling and lysis of specific groups of neurons. This pathological cell death can be induced by mutations in a family of genes including deg-1, mec-4 and mec-10 (degeneration and mechanosensory abnormal, respectively). These genes, called degenerin genes, encode subunits of a newly identified class of ion channels. Degeneration appears to occur as a consequence

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