Central Axonal Development and Pathology in Early Life

Abstract

Critical to brain development is the proper growth and maturation of the axons underlying neuronal circuitry and communication throughout the nervous system. During development, the axon undergoes a remarkable process of outgrowth from the cell body, elongation, pathfinding to its target, differentiation of its synaptic junction, and establishment of connections with dendritic and/or somatic synapses. In the human brain, the most dramatic period of axonal development is midgestation to the end of the second year of life (i.e., the period when the brain itself attains approximately 80% of its adult weight). During this period, the developing axon is especially vulnerable to different types of injury as it undergoes rapid elongation and differentiation. In this chapter, we review critical aspects of axonal development and pathology in early human life with a focus on the central nervous system. These aspects include the initial growth of the axon, the pathfinding mechanisms by which the axon locates the proper target, elimination of axonal connections to ensure the correct axon-to-target balance, and maturation of the axons to ensure proper transmission of signal, as well as the susceptibility of the developing axon to injury and selected disorders of axons in the developing human brain.