Neurogenesis, neuronal migration, and axon guidance

Abstract

Development of the central nervous system (CNS) is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical factors from early embryonic stages to postnatal life. Duringthe past decade, great strides have been made to unravel mechanisms underlying human CNS development through the employment of modern genetic techniques and experimental approaches. In this chapter, we review the current knowledge regarding the main developmental processes and signaling mechanisms of (i) neurogenesis, (ii) neuronal migration, and (iii) axon guidance. We discuss mechanisms related to neural stem cells proliferation, migration, terminal translocation of neuronal progenitors, and axon guidance and pathfinding. For each section, we also provide a comprehensive overview of the underlying regulatory processes, including transcriptional, posttranscriptional, and epigenetic factors, and a myriad of signaling pathways that are pivotal to determine the fate of neuronal progenitors and newly formed migrating neurons. We further highlight how impairment of this complex regulating system, such as mutations in its core components, may cause cortical malformation, epilepsy, intellectual disability, and autism in humans. A thorough understanding of normal human CNS development is thus crucial to decipher mechanisms responsible for neurodevelopmental disorders and in turn guide the development of effective and targeted therapeutic strategies.

Keywords: Axon guidance and pathfinding; Cortical development; Neural progenitor cells; Neurogenesis; Neuronal differentiation; Radial migration; Tangential migration.