Abstract
Mammalian development involves an exquisite choreography of cell division, differentiation, locomotion, programmed cell death, and senescence that directs the transformation of a single cell zygote to a mature organism containing on the order of 40 trillion cells in humans. How a single totipotent zygote undergoes the rapid stages of embryonic development to form over 200 different cell types is complex in the extreme and remains the focus of active research. Processes such as programmed cell death or apoptosis has long been known to occur during development to help sculpt organs and tissue systems. Other processes such as cellular senescence, long thought to only occur in pathologic states such as aging and tumorigenesis have been recently reported to play a vital role in development. In this review, we focus on apoptosis and senescence; the former as an integral mechanism that plays a critical role not only in mature organisms, but that is also essential in shaping mammalian development. The latter as a well-defined feature of aging for which some reports indicate a function in development. We will dissect the dual roles of major gene families, pathways such as Hox, Rb, p53, and epigenetic regulators such as the ING proteins in both early and the late stages and how they play antagonistic roles by increasing fitness and decreasing mortality early in life but contribute to deleterious effects and pathologies later in life.
Highlights
We focus on apoptosis and senescence; the former as an integral mechanism that plays a critical role in mature organisms, but that is essential in shaping mammalian development
Epigenetics can be broadly described as the changes made to an organism’s hereditary material which result in alterations of gene expression without changes to the DNA sequence (Goldberg et al, 2007)
The ability of ING1 to induce apoptosis in response to UV-induced DNA damage was dependent upon the PCNA-interacting Protein (PIP) motif of ING1 (Scott et al, 2001) while the ability of both ING1and ING2 to efficiently induce apoptosis via p53 depends largely on their polybasic regions that bind the bioactive stressinduced phospholipid phosphatidyl inositol 5 -monophosphate (Gozani et al, 2003)
Summary
Mammalian development begins with the fertilization of the female gamete, the ovum, by a sperm cell, the male gamete, forming a single celled zygote. The inner germ layer, the endoderm, gives rise to organs of the respiratory and digestive systems. The outer ectoderm germ layer gives rise to the central and peripheral nervous systems, hair, skin, nails, the mouth, the nasal cavity, the lens of the eye and various exocrine glands (Sasai and Robertis, 1997). Senescence has been proposed to play roles in development of the placenta (Rajagopalan and Long, 2012; Chuprin et al, 2013) and embryo (Davaapil et al, 2017), functioning mainly in tissue remodeling (Nacher et al, 2006; Muñoz-Espín et al, 2013; Storer et al, 2013; Zhao et al, 2018; Gibaja et al, 2019) and beginning early in evolution (Villiard et al, 2017), but how this occurs is not yet fully understood
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