Figure 1. Temporal stages and progenitor types in the human developing neocortex.

During early human brain development, a layer of neuroepithelial cells (NECs), spanning from the ventricular surface to the pial surface, populates the developing neural tube and undergoes self-renewing divisions to generate more NECs (symmetric divisions) in early developmental stages. They then elongate and differentiate into radial glial cells (RGCs), which also undergo symmetric divisions to expand the population of progenitors. During the neurogenic period, RGCs begin to divide asymmetrically to generate neurons while self-maintaining the progenitor pool, either generating neurons directly or producing neurons indirectly through intermediate progenitor cells (IPCs). Apical radial glial cells (aRGCs) are defined by residing in the ventricular zone (VZ) and by establishing contacts at both the apical and basal surfaces of the developing cortex. Later in development, aRGCs can also give rise to basal radial glial cells (bRGCs) by delamination of the apical belt of adherens junctions attached to the ventricular surface and translocation of their somas to the subventricular zone (SVZ). Based on marker expression, bRGCs have multiple subtypes, including HOPX+ bRGCs. Migrating neurons generated by aRGCs or bRGCs use the RG scaffold of both types of progenitors to migrate through the intermediate zone (IZ) into the developing cortical plate (CP), which contributes to the growth of the CP. By the second trimester of pregnancy (gestational week 17), aRGCs transform into truncated RGCs with their basal process terminating in the border between the inner and outer layers of the SVZ (iSVZ/oSVZ); thus, the RG scaffold becomes truncated at the iSVZ/oSVZ border. Cortical neurons are born in an inside-out fashion, with neurons destined to deeper layers (L6) born first and neurons destined to superficial layers (L2) born last. Density plots shown on the bottom represent the different neurogenic stages that preferentially generate neurons committed to each cortical layer. The extended neurogenic period for superficial layer neurons (L2–3), coincides with the expansion of bRGC proliferation and is considered a hallmark of human brain evolution.