The cerebral cortex is arguably the most complex structure in the mammalian brain. It develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved in this daunting process of cell diversification remain poorly understood. We recently described a novel pathway by which mouse embryonic stem (ES) cells, cultured in the absence of any added morphogen but in the presence of a Sonic Hedgehog inhibitor, can recapitulate the major milestones of cortical development observed in vivo. In this system cortical-like progenitors seem to follow an intrinsic pathway to generate a surprisingly diverse repertoire of neurons that display most salient features of bona fide cortical pyramidal neurons. When grafted into the cerebral cortex in vivo, these neuronal populations develop patterns of axonal projections highly similar to those of native cortical neurons. The discovery of intrinsic corticogenesis, from stem cells to cortical circuits, sheds new light on the mechanisms of neuronal specification, and may open new venues for the modelling of cortical development and diseases, and for the rational design of brain repair strategies.
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