Apoptosis in Developmental Processes

Abstract

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 system 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. Learning more about cell death in embryos will help us to understand how it is controlled in adults.

Heterogeneity of Cell Death

“…Cell death can be induced by multiple factors, including changes in local morphogens, hormonal change, signals from neighboring cells, mechanical damage, or drug treatment [Entezari et al, 2010]. Apoptosis occurs as an extrinsic and intrinsic process [Galluzzi et al, 2012].…”

Turning death into creative force during biofilm engineering

“…The new findings about the creative role of cell death during biofilm formation might provide valuable insights on why apoptosis is important for embryonic development (18). Drawing on the parallels between the two systems suggests that bacterial regulated cell death might be a rudimentary form of apoptosis.…”

Regulated cell death in diagnostic histopathology

“…MOMP, mitochondrial outer membrane permeabilization; IMS, inter membrane space; AIF, apoptosis inducing factor; ENDOG, endonuclease G; TNFa, Tumor Necrosis Factor alpha; TRAIL, TNF-related apoptosis inducing ligand; RIP1, Receptor interacting protein 1; RIP3, Receptor interacting protein 3; Smac/DIABLO, second mitochondria-derived activator of caspase/direct IAP binding protein with low Pi; CYTC, Cytochrome C; TNFR1, Tumor necrosis factor receptor 1; DCC, Deleted in Colorectal Carcinoma; DISC, Death Inducing Signaling Complex tissue remodeling, the formation of hollow organs and the neural tube, and the generation of sexual organs (Jacobson et al, 1997), shaping forms (e.g. interdigital clefts) and separating, splitting or allowing tissue layers to fuse (Entezari et al, 2010, Penaloza et al, 2006. During development, PCD is particularly prominent in central nervous system and the immunogenic cells of the hematopoietic system.…”

“…Exposure of intrauterine developing human embryo to noxious stimuli may cause cell stress and inappropriate or excess apoptosis, resulting in teratogenic effects (Brill et al, 1999, Entezari et al, 2010.…”