The specification of neuronal subtypes in the cerebral cortex proceeds in a temporal manner; however, the regulation of the transitions between the sequentially generated subtypes is poorly understood. Here, we report that the forkhead box transcription factor Foxg1 coordinates the production of neocortical projection neurons through the global repression of. a default gene program. The delayed activation of Foxg1 was necessary and sufficient to induce deep-layer neurogenesis, followed by a sequential wave of upper-layer neurogenesis. A genome-wide analysis revealed that Foxg1 binds to mammalian-specific noncoding sequences to repress over 12 transcription factors expressed in early progenitors, including Ebf2/3, Dmrt3, Dmrta1, and Eya2. These findings reveal an unexpected prolonged competence of progenitors to initiate corticogenesis at a progressed stage during development and identify Foxg1 as a critical initiator of neocorticogenesis through spatiotemporal repression, a system that balances the production of nonradially and radially migrating glutamatergic subtypes during mammalian cortical expansion. The functional integrity of the mammalian neocortex relies on precisely controlled neuronal production during development; however, how the transitions between the sequentially generated subtypes are coordinated remains largely unknown. Hanashima and colleagues now identify a program in which Foxg1 acts as a key regulator of the onset of projection neuron production through spatiotemporal repression. This unique mammalian system is adaptable to changes in cortical size and balances the production of nonradially and radially migrating glutamatergic subtypes during mammalian cortical expansion.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)