Cell Death during Developmental Processes

Embryonic development and differentiation to adult form depends on orchestration of cell division and death. In embryos, programmed death sculpts form, opens lumens, separates or splits tissue layers, allows tissue layers to fuse and removes vestigial organs. Both the central nervous and immune systems overproduce cells and destroy those that do not form successful synapses or produce unusable antibodies. Cell death is first seen in mammalian embryos when the blastocyst expands, but elsewhere, the first deaths are not seen before the maternal–zygotic transition. Abnormal timing, amount or localisation of cell death leads to abnormalities or death of embryos. Several signalling pathways trigger cell death. Usually, the signals activate caspases (first discovered in embryonic cell death in nematodes) and lead to apoptosis, although apoptosis is not the only form of cell death. The signalling mechanisms that control cell death in embryos are not well understood, but should be if we hope to understand normal and teratological development. Key Concepts Cell death can be seen in both embryonic development and normal growth of adult tissue. The embryonic cell deaths are highly programmed in that they are predictable in location, time and amount. In the simplest instances, such as in nematodes, control of cell death is under direct control of a small number of genes. Most but not all of the embryonic deaths are apoptotic. Embryonic cell to sculpt the embryo and define the boundaries of tissues and organs. In the central nervous system and the immune system, overgrowth (production of excessive cells) and subsequent pruning by cell death generate the high specificity that characterises these systems. Deregulation of apoptosis can produce many embryonic abnormalities and teratologies and, later in life, produces cancers, autoimmune disease or neurodegenerative disease. There are many means to study cell death, but only a few are directly applicable to the study of cell death in embryos. Nevertheless, further study is needed to understand the signalling mechanisms that decide the death of cells in specific locations and times. Autophagy is increasingly recognised as a factor influencing the likelihood of onset of apoptosis and cell death. New ultra-resolution fluorescence microscopic techniques, capable of simultaneously analysing energy flux, autophagy and apoptosis, may lead to new insights into these questions. Learning more about cell death in embryos will help us understand how it is controlled in adults. Keywords: apoptosis; autophagy; caspase; cell death receptor; embryo; embryonic development; gene expression; programmed cell death; techniques