Cell Death in Development

that the morphology of liver cells exposed to toxins, and Boston, Massachusetts 02115 lymphocytes treated with hormones, was the same as that described by the embryologist Glucksmann earlier Physiological mechanisms of cell death are used by in the century, they coined a new term, " apoptosis, " for multicellular organisms for development and morpho-cell deaths with this distinct morphology—whether they genesis, to control cell number, and as a defensive strat-be in response to physiologic or pathologic stimuli egy to remove infected, mutated, or damaged cells. Cell (Glucksmann, 1951; Kerr et el., 1972). death is required for the normal development of almost Although the first component of a cell death mechanism to be recognized was the mammalian gene Bcl2 all multicellular organisms and commonly involves the (Vaux et al., 1988), the first evidence that a genetic pro-production of excess cells and removal of those that gram existed purely for physiological cell death came are superfluous. Frequently in plants, and occasionally from studying development in C. elegans (Horvitz et al., in other organisms, cytoplasmic or structural compo-1982; Ellis and Horvitz, 1986). The ability of human Bcl2 nents of the dead cell serve important functions. The to prevent programmed cell death in C. elegans showed process of cell death used by metazoans for develop-that apoptosis in mammalian cells and programmed cell ment is highly conserved and is morphologically recog-death in the nematode were the same highly conserved nizable as apoptosis. The evolution of multicellularity process (Vaux et al., 1992). and cell specialization brought with it a need for the regulation of cell death by intercellular signaling. The Types of Cell Death mechanisms that implement developmental apoptosis While most developmental cell deaths in metazoans are may have originated from cell-autonomous cell death mediated by a family of cysteine proteases termed cas-processes used for defense. While the apoptosis ef-pases (Alnemri, 1997), there are a number of other ways, fector mechanisms have been extensively character-some of which are physiological, in which cells can die. ized, understanding of the pathways that signal and For example, if the gene for the caspase CED-3 is mu-control developmental cell death is far from complete. tated in C. elegans, death of the 131 somatic cells that When a cell in an organism dies due to a process are normally programmed to die during development encoded by that organism for the purpose of killing does not occur (Ellis and Horvitz, 1986), but …