Apoptosis in Development

Development involves a delicate orchestration of cell division, movement, differentiation, and death. Cell death in mammalian embryogenesis occurs as early as inner cell-mass differentiation, and it continues to be part of the developing embryo during the formation and functional completion of the different organs (1 -3 ). The importance of cell death was first recognized by developmental biologists and teratologists (4 ,5 ). More recently, with the new recognition of its possible role in many other areas such as aging, infectious diseases, and cancer, the field has received a burst of energy and, therefore, many investigators are in search of the signals that regulate cell death. The goal of this quest is to identify the dead or dying cells. The ability to identify and characterize the type of cell death has increased interest in cell death under different circumstances. Cell death has been divided into different classes based on the morphology and biochemical function of the cell during its demise. In necrotic cell death, which is not programmed, the cell typically loses energy resources or membrane integrity, swells, and osmotically lyses, losing or destroying contents in a chaotic manner (6 ). In programmed cell death, the cell appears to participate in its own demise. This type of cell death has been further divided into type I and type II cell death. In type I (apoptosis), a characteristic coalescence and margination of chromatin, related to degradation of the DNA ultimately to a nucleosomal ladder, is an early and prominent feature (7 ). In type II, although the nuclear collapse eventually occurs, it typically is late and modest, well preceded by many cytoplasmic changes. In cells with large amounts of cytoplasm, these changes likely include lysosomal (autophagic) degradation of massive amounts of cytoplasmic constituents (8 ,9 ). Although there are specific markers unique to each type of cell death, there are many gray areas and points of overlap, reflecting the different cell types that might undergo cell death.