Figure 4.

(A) The neuro-ontogenic process starts at gestational age (GA) weeks 2–3 with the constitution of the neural tube. At GA week 4, the rostral portion of the neural tube forms the prosencephalic, mesencephalic, and romboencephalic vesicles. The prosencephalic vesicle then forms two vesicles that are destined to become the telencephalon and the diencephalon (thalamus, hypothalamus, and other structures). The schematic diagram represents the development of telencephalon. Initially, the telencephalic primordium is constituted by dividing neuroepithelial cells (often called neural stem cells), characterized by interkinetic nuclear migration, which form the ventricular zone (VZ). There, one type of cells, the radial glial cells, is particularly prominent and distinctive. At GA week 4, they undergo to an early exponential proliferation increasing the number of progenitor/intermediate progenitor cells and the thickness of VZ. Early born neurons are interneurons which move within the marginal zone (MZ) and intermediate zone (IZ). The MZ will eventually form cortical layer I and, for some authors, MZ could be identified also before the cortical plate (CP) formation as early MZ (eMZ). The IZ is a cell-sparse compartment and exists before the appearance of the CP. Radial glial cells and intermediate progenitor cells can be classified in two distinct subpopulations: apical, resident in VZ with bipolar fibers, and basal, which delaminate from VZ with unipolar basal fiber. Apical progenitor cells in the VZ and basal progenitor cells in subventricular zone (SVZ) are considered the main source of pyramidal neurons. Around GA week 5, the neurogenesis begins and the neuronal precursors proliferate rapidly within the VZ. The neurons located in the first recognizable cortical layer, known as the preplate (PP), form the earliest synaptic connections. PP is a transient structure present before the appearance of the CP. Around week 7, the PP cells contribute to the subplate (SP) which remains below the CP after its formation and contains post-migratory pyramidal neurons and interneurons. Moreover, the accumulation of basal progenitor cells creates a distinct new compartment above the VZ, the SVZ. Here, they divide and are considered an additional source of intermediate progenitor cells. By GA week 8, radially migrating neurons from VZ and SVZ initiate the development of the layered CP forming from inside to outside. For example, pyramidal neurons eventually migrate outward along the radial glial cells. (B) Timeline of the neurobiological processes in the telencephalon and the sensory/motor connectivity during human ontogeny. The weeks of gestational age (GA) are reported and related to the major events during fetal neural development: neuronal proliferation; neural migration; synaptic connections; myelination; cortex (mature shape organization); thalamocortical connectivity (spinothalamic tract); cortico-spinal connectivity; functionally expressed as cortical integrated activity (REM-non-REM sleep cycles).