Chapter 14: Development of the Nervous System

The development of the entire nervous system, including the special sense organs, fundamentally originates from three populations of the early epiblast: the neural plate, giving rise to the central nervous system (CNS), somatic motor nerves, and preganglionic autonomic nerves; the neural crest cells, which undergo epithelial to mesenchymal transition and migrate widely to form the peripheral nervous system (PNS), encompassing most neurons and glia of the PNS, somatic and autonomic ganglia, and significant mesenchymal populations in the head; and ectodermal placodes, focal thickenings of the head ectoderm that contribute cells to cranial sensory neurons and form specialized epithelia like the inner ear and olfactory system. The process of forming the neural tube, known as neurulation, occurs in two main ways: primary neurulation forms the rostral tube by the folding of the neural plate, while secondary neurulation forms the caudal segment through the aggregation and mesenchymal to epithelial transition of caudal eminence cells. Failures in these processes lead to critical conditions such as anencephaly and spina bifida. Early brain structure develops through regional expansions—the prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain)—and is contoured by flexures, notably the mesencephalic, cervical, and pontine bends. The rhombencephalon is segmented into units called rhombomeres, which are crucial for subsequent patterning, including directing neural crest cell migration into the pharyngeal arches. Histologically, the neural tube walls differentiate into the ventricular, intermediate (mantle), and marginal zones, with dorsoventral polarity established by the notochord inducing the ventral floor plate, which separates the motor-producing basal plate ventrally from the sensory/interneuron-producing alar plate dorsally. In the cerebral hemispheres, neuroblasts are generated in the ventricular and subventricular zones and migrate radially along radial glial processes to form the cerebral cortex layers in an inside-out progression, establishing a transient, circuit-integrating layer known as the subplate. Conversely, GABAergic inhibitory interneurons migrate tangentially from the medial and lateral ganglionic eminences. The vascular supply develops through angiogenesis, featuring ventriculopetal arteries serving the cortex and ventriculofugal arteries serving the ventricular zone, a highly proliferative area known as the germinal matrix. This zone is susceptible to circulatory perturbations, particularly in premature infants, leading to white matter injuries like periventricular leukomalacia or intraventricular hemorrhage. Postnatal brain maturation is characterized by rapid growth, extensive myelination (by CNS oligodendrocytes and PNS Schwann cells), and the pruning of synaptic connections, a schedule that is protracted in humans compared to other primates, contributing to prolonged plasticity and reliance on the close mutual interactions described within the mother-infant dyad for optimal neurodevelopment.