Apoptosis or Programmed Cell Death

Apoptosis is an important cellular process that allows cells to die in a programmed and organized fashion. This form of programmed cell death is crucial to the stability and equilibrium of living organisms. Such a process is shared amongst vertebrates and invertebrates alike (Miguel-Aliaga et al., 2009). It is easiest to define “normal” development by observing that which is understood as abnormal. Programmed cell death is understood to have a distinguishable relationship with cell division and differentiation. If they are not kept at equilibrium, abnormalities can occur.

Cell proliferation—the increase in number of cells as a result of cell growth and division—and PCD maintain the homeostasis of the body. If the intricate balance between the two is disrupted, the normal development of the organism is put into jeopardy. Recent studies have sought out to understand the role that apoptosis plays during neurodevelopment and its relationship to neurodevelopment. This paper will address the importance of apoptosis in prenatal development as well as highlight examples of occurrences where apoptosis is not regulated. This paper will then situate apoptosis within the larger conversation of the field of developmental psychobiology, the fields importance, and will discuss implications for understanding it.

What is Apoptosis?

Apoptosis, or programmed cell death (PCD), is when a cell commits suicide. This, then, activates an intercellular death program. PCD occurs in both pre and post natal development. It occurs everywhere in the developing vertebrate nervous system. It occurs most extensively in the early stages of vertebrate neural development (Miguel-Aliaga et al., 2009). Such PCD occurs in high density proliferated areas of the developing nervous system (Blaschke et al., 1996). An example of PCD can be visualized in figure 1, where in similar fashion to human fetal development, mouse paws are sculpted by cell death during the embryonic development. Said paws start off as webbed and each “finger” is further defined only as the cells between them die (Alberts et al., 2002).

How does Apoptosis work?

Cells that undergo apoptosis go through what is considered an orderly process (see Figure 2). The designated cell shrinks and develops bubble-like lumps (i.e. blebs) on their surface. The chromatins condense, and the DNA and organelles begin to break down into small fragments as well. After the membrane of the cell also blebs, the fragments begin to also neatly move towards the blebs and thus break apart and create the apoptotic bodies. The apoptotic bodies then release signals that attract phagocytic immune cells such as, macrophages to “clean up” and eat the cell fragments.

Within the process of apoptosis, the cell is broken down from within. Caspase proteins—proteins which carry out the cell death—can be activated in two distinct ways. The first is the extrinsic pathway. In this pathway, the designated cell receives death signals from neighboring cells. These signals are latched on to death receptors of the designated cell, that then connect to the FAS associated death domain (FADD). In the final step of this pathway FADD activates caspases that then begin the caspases cascade. Once all the caspases are activated, apoptosis occurs. The second pathway, is when signals of cell death come from within the cell itself. When a cell has irreparable damage, or stops receiving survival signals, contents from the mitochondria leak out to the cytoplasm. In this pathway, the leakage solicits the caspase cascade that then triggers apoptosis (Thouvenot-Nitzan, 2016).

Evolution of the Discipline

Darwin’s theory of evolution played an influential role in the formulation of developmental psychology. It was through Darwin and the theory of evolution that both disciplines of biology and psychology began to reject ideas that humans could be neatly divided into “a psychological mind or soul and a biological body” (Michel and Moore, 1994). Traditionally, psychology as a discipline was concerned with how to describe and analyze the structure of the mind. However, after the boom of evolution theory, the question began to shift and gear more towards the functions of various mental processes (Michel and Moore, 1994). Psychology went from a sort of philosophical discipline, to attempting to be in conversation with biology and understand behavior and development in a more nuanced way. This paradigmatic shift, thus, gave room for the behaviorist movement that focused primarily on what could be observed—not on what could be presumed based off of stories. It is argued that before the behaviorist movement, psychologists did not have a means to actually study development, particularly choosing and using children to do so (Michel and Moore, 1994). This does not mean, however, that there were not formulations of thought surrounding how development works.

One of the earliest modes of thinking about development was preformationism. Preformationists believed that there is no development, but rather everything is prepackaged and formed from the very beginning. This ideology presupposed that children were small replicas of adults. Preformationists believed that there was no distinction between children and adults. Figure 3 shows visual representations of preformationism. This idea, was then gradually replaced by predeterminsim, which supposed that development is a predestined and organized occurrence that happens in distinct stages (Michel and Moore, 1994). Through this paradigm, people began to understand development as a sequence of change over ones’ life span.

As the authors of the textbook Developmental Psychobiology suggest, “Because Darwin’s theory was designed to account for diversity among the various life forms, and because development within a single life span also includes changes and continuity, some of those who attempted to understand the changes revealed by the predeterminist approach looked to the notion of evolution for useful explanations of individual development.” (Michel and Moore, 1994). One of these scientist was Haeckel, an embryologist, who believed that what occurred in embryo was actually reflections of the species’ phylogenetic past. Haeckel’s law, then, became well understood by the phrase “ontogeny recapitulates phylogeny”.

Scientists like G. Stanley Hall, attempted to apply Haeckel’s recapitulation theory to human psychological development. Hall focused on children and the ways he could observe the progression of things like reflexes and instinct, to planned behavior. Hall was not the only one to begin to apply this understanding of development as a progression and applicable to humans. Scholars like Jean Piaget and Heinz Werner, began to construct understandings of cognitive development in a similar fashion: with different stages that occur in early child life (Evans, 2019).

Problematics with Haeckel’s law

Haeckel’s law determined that the development of an individual organism recapitulates the development of it species. Put in other words, the embryo “retraces in abbreviated form during development all of the evolutionary changes that it’s ancestors have gone through” (Michel and Moore, 1994). However, what Haeckel’s law did no take into account, was that while some ancestral structures can appear in early embryonic development and then later disappear, “adaptations that take place over individual development are proximately adaptive, and cannot be confused with evolution” (Evans, 2019).

Understanding Apoptosis in Practice

It is presumed by some in the field that apoptosis holds an evolutionary advantage. That as a more complex nervous system evolved, so did the need for the body to be able to clean up or get rid of abnormal or unneeded cells (Miguel-Aliaga at al., 2009). This is supported by studies that have found a positive correlation between cell proliferation and PCD in different organisms (Miguel-Aliaga at al., 2009). With up to 50% of cells dying shortly after being created in humans (Margolis et al., 1994) and 10% in nematode canorhabitis elegan (c. elegan) (Miguel- Aliaga et al., 2009).

Alcohol has been a well determined and documented teratogen that is able to cause a variety of deficiencies and complication in children with prenatal exposure to it (Dunty et al., 2001; Prock et al., 2007). Fetal alcohol syndrome (FAD) induced abnormalities include mental retardation, attention deficient disorder, and dysfunction of the central nervous system (CNS) (Dunty et al., 2001; Prock et al., 2007). Prior studies have indicated that an important feature to ethanol-induced malformation, is cell death. The disruption of the timing of PCD can result in “dymorphogenesis” (Dunty et al., 2001) on patterns of PCD. In a particular study, Dunty (2001) and his colleagues analyzed ethanol dosages in mice, in gastrulation days equivalent to that of week 6 of human gestation. Researchers pointed out that, “this critical period of embryogenesis encompasses major morphogenic events including gastrulation, neurulation, and organogenesis” (Dunty et al., 2001). This study found that in sites of normal apoptosis, ethanol resulted in excessive cell death in crucial cell populations like the neural crest. These findings suggest that cell death is a mechanism through which to understand biologically how our bodies handle discrepancies, and what can occur when it cannot.

Apoptosis within developmental psychobiology

In the Michel and Moore (1994) chapter that we read for class they said, “developmental psychobiology has developed as a discipline that integrates information drawn from evolutionary and developmental biology, physiology and other areas of biology with various sub disciplines of psychology to address developmental questions and behavior.” Ultimately, the purpose of developmental psychobiology is to take an interdisciplinary approach to understanding development. If one were to attempt to study a phenomenon from just one perspective—psychology or biology—then one does not receive the full story or picture. Rather, it is the ways in which these two disciplines are in conversation with one another, that we are able to understand the nuances of development, its inner workings as well as how they manifest.

Apoptosis is a primal example of how developmental psychobiology is important. Abnormal neuronal loss is increasingly being recognized as an important pathological feature to neuropsychiatric disease’s like Alzheimer’s, Parkinson’s, Fragile X syndrome, and Schizophrenia (Margolis et al., 1994). PCD, then, is a biological mechanism that can be understood to create conditions for deficiencies in development and behavior, if homeostasis with cell proliferation is not maintained.

PCD can be critiqued as an evolutionarily preserved tool that is meant to regulate our bodies. As a process, it can both undermine and support predeterminist thought. Each cell is encoded with the mechanisms for cell suicide. In normal development, PCD of particular cells is predetermined. However, as this paper suggests, when cells are presented with external influences like teratogens, PCD is not able to regulate itself. In this way, PCD trumps predeterminism’s understanding of predestined progression to a better person (Michel and Moore, 1994). Ultimately, the role of PCD in development, should not be undervalued. It plays a pivotal role in understanding the intersections of biology and psychology.

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