Human neocortical development: the importance of embryonic and early fetal events

The identification of numerous genes involved in the development of the cerebral cortex has led to an increased interest in the early stages of corticogenesis, when the first postmitotic neurons migrate into the cortical plate to form the foundation of the adult cortex. However, the cellular substrate of gene expression in early human cortical development is widely unknown. This article analyzes the complex sequence of events in the differentiation of the preplate, the predecessor of the neocortex, and discusses the possible origin and migratory routes of the neuronal populations involved in the transition from preplate to cortical plate. The neuronal classes present in embryonic and early fetal stages are redefined in terms of their relationship with the Reelin-Dab1 signaling pathway whose integrity is essential for successful migration into the cortex. A timetable of developmental steps is provided, and the peculiarities of the preplate derivatives in the human brain, marginal zone, and subplate are discussed. The results presented here may contribute to a deeper understanding of the pathogenesis of migration disorders.