Cerebral cortex development: an outside-in perspective

The cerebral cortex is a complex structure that contains different classes of neurons distributed within six layers and regionally organized into highly specialized areas. Cortical layering arises during embryonic development in an inside-out manner as forebrain progenitors proliferate and generate distinct waves of interneurons and projection neurons. Radial glial cells (RGCs) derive from neuroepithelial cells and are the founding cortical progenitors. At the onset of corticogenesis, RGCs expand their pool by proliferative divisions. As corticogenesis proceeds, they gradually undergo differentiative divisions to either generate neurons directly (direct neurogenesis) or indirectly via production of intermediate progenitors that further divide to generate pairs of neurons (indirect neurogenesis). The fate of RGCs is finely regulated during all the corticogenesis process and depends on time-scaled perception of external signals and expression of intrinsic factors. The present Review focuses on the role of physiological extracellular cues arising from the vicinity of neural progenitors on the regulation of dorsal neurogenesis and cerebral cortex patterning. It further discusses how pathogenic viral factors influence RGC behaviour and disrupt cerebral cortex development.