Résumé : The cerebral cortex develops through the coordinated generation of dozens of neuronal

subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic

stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor,

recapitulate in vitro the major milestones of cortical development, leading to the sequential

generation of a diverse repertoire of neurons that display most salient features of genuine

cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop

patterns of axonal projections corresponding to a wide range of cortical layers, but also to

highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that

the identity of a cortical area can be specified without any influence from the brain. The

discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal

specification, and opens new avenues for the modelling and treatment of brain diseases.

In a further attempt to prove the validity of this model, we have initiated the study of the

mechanism of action of FoxG1, a forkhead box transcription factor involved in the control of

cell fate decision in the developing cortex.