FIGURE 1.

Critical milestones of human corticogenesis and associated NDDs. The human cerebral cortex begins to form by symmetric division of neuroepithelial cells (NECs, bright gray) in the first trimester, which elongate in shape to convert to radial glial cells (RGCs, dark gray). RGCs increase in number, asymmetrically divide and convert to outer radial glial cells (oRGCs) also known as basal RGCs, or give rise to neuronal intermediate progenitor cells (nIPCs), again by asymmetric division. The latter further divide symmetrically to give rise to young excitatory principal neurons (pink), which migrate from the subventricular zone (SVZ) toward the forming cortical plate (CP). Inhibitory interneurons (brown) invade the developing neocortex along the marginal zone (MZ) or the subplate (SP) and SVZ, before they switch to radial migration to enter the cortical plate. Increased progenitor and neuronal numbers as well as rapidly expanding neuronal networks contribute to physical stress, forming the main gyri at the end of the second trimester. At later stages of corticogenesis, intercellular connections begin to form, for which morphological differentiation and defined setting of neuronal proportions are necessary. Failures of corticogenesis are suggested to contribute to various NDDs with respect to the given time point and affected process, which is depicted on the bottom for different examples of diseases. CP = cortical plate; iSVZ = inner subventricular zone; IZ = intermediate zone; MZ = marginal zone; NE = neuroepithelium; oSVZ = outer subventricular zone; SP = subplate; VZ = ventricular zone.