Cell death in animal development

Abstract

Cell death is an important facet of animal development. In some developing tissues, death is the ultimate fate of over 80% of generated cells. Although recent studies have delineated a bewildering number of cell death mechanisms, most have only been observed in pathological contexts, and only a small number drive normal development. This Primer outlines the important roles, different types and molecular players regulating developmental cell death, and discusses recent findings with which the field currently grapples. We also clarify terminology, to distinguish between developmental cell death mechanisms, for which there is evidence for evolutionary selection, and cell death that follows genetic, chemical or physical injury. Finally, we suggest how advances in understanding developmental cell death may provide insights into the molecular basis of developmental abnormalities and pathological cell death in disease.

Programmed Cell Death Not as Sledgehammer but as Chisel: Apoptosis in Normal and Abnormal Craniofacial Patterning and Development

“…Among the developmental mechanisms necessary for normal vertebrate morphogenesis are (1) epithelial invagination and evagination, (2) closure of epithelial tubes and vesicles, (3) separation of tissue components, (4) migration of anlage and rudiments, (5) the conjoining of appositional anlage, (6) the regulation of tissue specific cell-population size, and (7) the removal of only transiently necessary (or vestigial) tissues. As we will discuss below, the ontogenetic topography of such processes often correlates with the temporospatial topography of apoptosis (Glücksmann, 1951;Saunders, 1966;Kerr et al, 1972;Jacobson et al, 1997;Fuchs and Steller, 2011;Ghose and Shaham, 2020;Voss and Strasser, 2020). As an evolutionarily conserved mechanism of organismal cellular auto-culling, apoptosis results in a controlled, distinct, canonical and readily recognizable set of changes in cellular ultrastructure.…”

Role of Cell Death in Cellular Processes During Odontogenesis

“…The intrinsic pathway is activated as a response to cellular stress and involves the permeabilization of mitochondria and the release of Cytochrome c (Moffitt et al, 2010;Nair, 2010;Bali et al, 2013;Ghose and Shaham, 2020). Members of the Bcl2 gene family regulate the intrinsic pathway of apoptosis, acting through several proteins, both anti-(Bcl2, BclXL, Bclw, Mcl1, and A1) and pro- (Bax,Bak,Bok,Bad,Bid,Bik,Blk,Hrk,BNIP3,and BimL) apoptotic proteins, forming heterodimers to modulate each other's function (Strasser et al, 2000;Zimmermann et al, 2001;Fan et al, 2005;Ghose and Shaham, 2020). Bax permeabilizes the outer mitochondrial membrane and facilitates the release of Cytochrome c, along with fragmentation of the mitochondrion itself (Youle and Karbowski, 2005).…”

“…Bax permeabilizes the outer mitochondrial membrane and facilitates the release of Cytochrome c, along with fragmentation of the mitochondrion itself (Youle and Karbowski, 2005). Bcl2, on the other hand, inhibits apoptosis by blocking the release of Cytochrome c from mitochondria (Kitamura et al, 2001;Youle and Strasser, 2008;Ghose and Shaham, 2020). After release, Cytochrome c subsequently forms a multi-protein complex known as the apoptosome with Apoptotic protease activating factor 1 (APAF1).…”

Orchestration of Force Generation and Nuclear Collapse in Apoptotic Cells

“…Apoptosis, also known as programmed cell death, is the cellular process by which cells die in a coordinated fashion, supposedly with limited immunological impact, if any [ 8 ]. Apoptosis is orchestrated by caspases, cysteine proteases that are highly conserved across evolution [ 9 ]. Intrinsic or extrinsic death signals, e.g., TNF-alpha, converge on activation of upstream caspases that, in turn, cleave and activate executioner caspases, such as caspase-3, 6 and 7.…”