Regulatory mechanisms of cortical laminar development

The developing forebrain exhibits a high degree of spatiotemporal regulation of proliferation and cell cycle exit in progenitor cells of its proliferative zones. This results in the balanced deployment of progenitors between asymmetric division, yielding postmitotic neurons and cycling progenitors, and terminal symmetric division, resulting in differentiated daughter cells. Radial glia have been demonstrated to be the principal neuronal progenitor of the cortical primordium. Lineage tracing studies employing real-time imaging in vivo have enhanced understanding of neuronal production and migration. Cortical projection neurons have been shown to arise from the radial migration of precursors generated in the dorsal telencephalon, whereas most interneurons derive from the germinal zone of the ventral telencephalon and migrate tangentially into the primordial cortex. Cells from both populations undergo diverse and complex sequences of migratory activity. Neuronal phenotypic potential is informed in progenitors prior to their last cell division. Laminar and regional fate potential of progenitors becomes progressively restricted with successive cell cycles. This process of neuronal fate specification is regulated by the interaction of programs of transcriptional regulation with extrinsic patterning signals according to time and region of the proliferative zone in which the final mitotic cycle occurs.