Cell Migration in the Mammalian Cortex

Abstract

One of the hallmarks of the developing central nervous system (CNS) is the migration of diverse newly born cells from embryonic germinal regions to their distant final destinations. Cell migration is an ongoing process from closure of the first CNS structure, the neural tube, through postnatal life. Precise cellular positioning as a result of normal migration directly contributes to anatomical formation of cortical layers (lamination), determination of brain size, and the acquisition of functional connectivity. Disruption of cellular migration by mutations or environmental insults can lead to structural changes of the cortex, as in malformations of cortical development, and abnormal neuronal activity resulting in functional changes, such as seizure activity or hypersensitivity for extrinsic stimuli as observed in patients with neurodevelopmental disorders (NDDs). Thus, our focus on cellular migration within the developing brain is essential for a deeper understanding of the complexity of brain development and for new approaches to treating NDDs.

The major cell populations within the mammalian neocortex – glutamatergic excitatory neurons (pyramidal neurons or projection neurons) and GABAergic inhibitory neuron (interneurons) along with non-neuronal microglia and oligodendrocyte precursors – exhibit remarkably distinct migratory features. In this chapter, we address the different migratory characteristics of these populations. In particular, we deal with their migratory strategies, routes, and the mechanisms for responding to diverse intrinsic or extrinsic signals. We also discuss how the errors of migration in the developing brain are associated with the occurrence of NDD, which include conditions such as autism spectrum disorders (ASD) and epilepsy.