Brain Development

Humans share many similarities with other animals, including the ability to experience sensations, exhibit motor behavior, and even socialize. However, we are clearly different in many important regards. For example, unlike any other animal, humans possess the unique ability to produce and understand language, experience complex emotions, and perform higher cognitive functions. Not surprisingly, each of these abilities is under the control of the brain. What this means, therefore, is that although the human brain is anatomically comparable to the animal brain in regard to “lower” structures required for the production of basic functions, the human brain also contains “higher” structures that produce the behaviors found exclusively in humans. As such, humans possess the most highly evolved brain. This is illustrated by the fact that on average the adult brain consists of 100 billion neurons, each of which makes between 1,000 and 10,000 connections with other cells. What is perhaps even more amazing is that despite its obvious complexity,  the  entire  human  brain  originates  from  a single cell, as does the rest of the human body. The following discussion will describe the process of human brain development, beginning at the time of conception and ending when all neurons have arrived at their appropriate target within the brain.

Early Central Nervous System Development

The human central nervous system begins to develop within 2 weeks after conception. Around this time, the single-celled embryo enters its blastulation phase, during which it undergoes a series of divisions leading to the formation of a hollow, multicelled ball called a blastula. The blastula then enters gastrulation, a process marked by the cells’ reorganization into three distinct layers: endoderm, mesoderm, and ectoderm. In contrast to the blastulation phase during which the embryo simply multiplies in size, the gastrulation phase is characterized not only by continued embryonic growth, but also by the first attempt at becoming a multistructured, multifunctional organism. This is evidenced by the fact that each of the three layers formed during gastrulation is exclusively involved in the formation of specific constituents of the human body. For example, the mesoderm gives rise to muscle, bones, connective tissue, and the cardiovascular system; the endoderm forms the gut and internal organs; and the ectoderm forms the skin and central nervous system (CNS).

Neurulation is defined by the creation of an indentation along the length of the ectoderm. It is considered the earliest stage of brain development and is complete by approximately 3 weeks following conception. During neurulation, cells on either side of the ectoderm’s “neural groove” thicken to form two folds that eventually fuse to create the neural tube. The tissue of the neural tube can be divided into two regions: the ventricular zone and the marginal zone. The ventricular zone is the innermost region of the neural tube. Its region is defined by its location (which is adjacent to the neural tube’s ventricle), as well as by the presence of neural and glial precursor cells (neuroblasts and glioblasts). All neuroblasts and glioblasts originate and proliferate in the ventricular zone. The marginal zone is the outermost region of the neural tube. It contains a certain type of cell of unknown origin that expresses reelin. Reelin is a substance critically required for normal cortical development and organization. Interestingly, although precursor cells neither reside nor divide within the marginal zone, they do transiently appear in this region throughout the development of the neural tube. Given the function of reelin in brain development, it is therefore likely that the transient expression of neural precursors in the marginal zone is to undergo some process necessary for normal brain development.

From Neural Tube To Brain: How Do Precursors Fulfill Their Destiny?

It is amazing that at only 3 weeks after conception the human embryo has developed to such a degree that it now contains all of the hardware necessary to create the entire human brain. What is perhaps even more remarkable, however, is that each neuron throughout the entire adult brain originates from the undifferentiated precursor cells that reside in the ventricular zone of the embryo’s neural tube. What this means is that the highly specialized neurons that mediate our sensory experiences, regulate our motor behavior, influence our cognitive abilities, and affect our emotional reactions can all be traced to the confines of the relatively primitive neural tube of the 3-week-old embryo. Moreover, given that each of the above functions (as well as the thousands of others not mentioned) is generally associated with distinct brain regions, the question arises: How is it that these cells find their way to their ultimate destination?

During the development of the neural tube, special cells called radial glia are also formed. The sole purpose of radial glia is to guide neuroblasts to where they are destined to belong. This is evidenced by the fact that radial glia are transiently expressed. During brain development, they are found in abundance. Once neuronal migration is complete, they essentially disappear. Like all neurons and glia, radial glia are also birthed and proliferate in the ventricular zone of the neural tube. However, radial glia are unique in that their fibers extend all the way to the pial surface of the neural tube, thus forming a scaffold-like structure. This scaffold provides a means by which neuroblasts can migrate from the ventricular zone to their final destination.

Neuroblasts do not simply attach to radial glia and blindly migrate out, however. Instead, they partake in an active process mediated by both genetic as well as environmental factors. Although each neuroblast is genetically predisposed to become a specific type of neuron, it ultimately reaches its destination by processing chemical information in the extracellular environment during its journey. The acquisition of chemical information is made possible by the unique morphology of migrating neuroblasts whose axon and dendrites have extensions called growth cones. Growth cones contain chemically sensitive receptors and tiny, fingerlike structures called filopodia that are used to pull the cell along the radial glia. During migration, the neuroblast is either chemically repelled or attracted to specific locations. Following these signals, it uses its filopodia to move along the radial glia toward the target to which it is attracted. Brain development is often referred to as occurring in an “inside-out” fashion in that the oldest neurons are located more deeply within the brain while the newest ones are found at the surface. This is because the first neuroblasts to migrate from the ventricular zone journey only a short distance before reaching their final target. As more new neuroblasts are birthed, they travel over all previous progenies to reach their targets, until the final set of neuroblasts arrives at the outermost layer of the brain.

The Influence Of Neural Communication On Brain Development

Once the neuroblast reaches its final destination, it is considered a neuron and defines itself as such by differentiating into the specific type of neuron it is determined  to  be.  That  is,  it  becomes  a  sensory neuron if it is destined to be involved in a sensory process or a motor neuron if it is destined to perform motor behavior. Arrival at its target also causes the neuron to seek out contact with other cells. This contact is achieved through the creation of synapses (synaptogenesis). A synapse is the tiny gap between neurons (neurons do not touch) and is the fundamental process by which information is communicated from cell to cell. Early in development, neurons send projections to a very general region and synapse with many more cells than is necessary. As the brain continues to develop, some synapses (the appropriate ones) are used more than others. This frequent communication between two neurons leads to the strengthening of that particular synapse and makes the connection more likely to be maintained. In contrast, those synapses that are rarely used become “pruned” away. The result of this process is a very precise connection from one neuron to another. Behaviorally, this process can be illustrated through the examination of infant motor development. For example, early in infancy when babies reach for objects, they often overshoot their target. However, with repeated attempts over time, their reach becomes more skilled and precise. The process by which synapses are maintained can also be illustrated morphologically. For example, although the adult human brain is greater in both size and weight than the developing brain, the developing brain actually contains many more neurons and synapses. This occurs because as the brain develops some regions lose as many as 80% of the cells that inhabit the region through the process of apoptosis (programmed cell death). Incidentally, apoptosis is regulated by a number of factors, one of which is the failure of the neuron to make appropriate synaptic connections. Presumably, if a neuron does not receive sufficient connectivity from other neurons it is not critically required for normal brain function. As such, it commits a sort of cell suicide in order to ensure that it does not get in the way of other activity.

Summary

Human brain development is truly an awesome process. From its origins of the ectoderm of the gastrula, to its evolution into a multibillion-celled organ, the brain develops in a tightly regulated process under heavy genetic as well as environmental control. Despite our vast understanding of the human brain, the fact that we are continually learning more about it and its processes is alone testament to its complexity. Clearly, scientists  for  years  to  come  will  continue  to  be amazed by the human brain.

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