Generation of cortical neurons from pluripotent stem cells

The cerebral cortex is the most complex structure in the mammalian brain, which develops through the coordinated generation of dozens of neuronal subtypes. Here, we review recent studies that show how embryonic stem cell (ESC)-based differentiation can recapitulate the major milestones of cortical development observed in vivo. ESC-derived cortical-like progenitors are able to generate a diverse repertoire of neurons that display most salient features of bona fide cortical pyramidal neurons of different layers. Importantly, when transplanted into the mouse cerebral cortex in vivo, these neuronal populations develop patterns of axonal projections highly similar to those of native cortical neurons. ESC-based corticogenesis, which can be applied to cells of mouse or human origin and to induced pluripotent stem cells, opens new perspectives for the modeling of cortical development and diseases and in the long run for the rational design of brain repair strategies striking the cortex.