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The human brain consists of 100 billion neurons that connect with more than 100 trillion synapses. The ability of neurons to form and modulate precise connections with one another is critical to every aspect of nervous system development and function. Adding to the complexity of the nervous system, glial cells (astrocytes, oligodendrocytes, microglia, and others) far outnumber neurons, and their contributions to critical brain functions are increasingly being appreciated. Malformation or dysfunction of even just a small subset of cells can manifest in neurologic symptoms. Understanding the essentials of the nervous system’s anatomy and function provides a robust basis for neurologic practice. Examining a patient who presents with a neurologic problem should lead the clinician to ask and answer 2 fundamental questions:

  1. What part(s) of the nervous system is/are affected?

  2. What is the nature of the dysfunction?

This approach requires the ability to localize different functions to distinct regions of the nervous system. Adding a layer of complexity, the pediatric neurologist is faced with the task of answering these questions in the setting of very dynamic changes that occur as a child’s nervous system matures. It is thus important to review the basic principles of pre- and postnatal brain development.

Over the past decades, studies in disparate fields such as molecular and cell biology, stem cell biology, genetics, neurochemistry, immunology, and imaging have shed light on the remarkable molecular and cellular bases of neurodevelopment. Spurring excitement for the neurosciences and their clinical application, we continue to learn more about the brain’s complexity as new tools are being developed. While much more needs to be learned, this chapter highlights some of the major advances in our understanding of normal brain development. Following the chronological order of development, the first part will highlight milestones of prenatal brain development such as the formation of the neural tube and regional patterning that will determine the major subdivisions of the central nervous system. The second part will review the mechanisms that lead to proper wiring of neurons in the cerebral cortex, the part of the brain responsible for most human behaviors. Finally, the third part will discuss the major subdivisions of the mature central nervous system and highlight emerging developmental links to neurologic diseases.

Normal neuronal development can be divided into a series of key steps: neurulation, regionalization, neurogenesis, migration, differentiation, apoptosis, axon guidance, synapse formation and pruning, myelination, and cortical folding. In these 10 steps, cells go from unspecified ectodermal constituents to highly differentiated neurons for which connections are being fine-tuned at the synaptic level. Neurodevelopment, however, does not stop with birth and extends through childhood, in fact likely throughout the whole life span.



The nervous system develops from a region of the ectoderm called the neural plate. During the third week of ...

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