Fig. 1.

Embryonic cortical neurogenesis occurs in an inside-out fashion. a In the developing dorsal telencephalon, radial glial precursors (RGPs) residing in the ventricular zone (VZ) adjacent to the lateral ventricles (LV) can give rise to a postmitotic neuron directly or indirectly via an intermediate progenitor (IP) cell. IPs populate the space basal to the VZ known as the subventricular zone (SVZ). Cortical neurons are generated in an inside-out fashion to populate the six layers of the cortex. Earlier-born neurons (shown in green and purple) populate the deepest of the six cortical layers (V–VI), while later born neurons (shown in red) populate progressively more superficial layers (II–IV). These layers contain distinct neuronal subtypes that differ based on morphology, electrophysiological activity, axonal connectivity, and gene expression. b Illustration of a cross-repressive transcriptional circuit that regulates deep versus superficial layer neuron specification [1, 4]. Tbr1 specifies deep layer VI corticothalamic neurons (shown in green) in part by repressing Fezf2, while Fezf2 acts upstream of Ctip2 to specify deep layer V subcerebral neurons (shown in purple) [1, 4]. Sox5 regulates the timing of deep layer neurogenesis by repressing Fezf2 until the production of layer VI corticothalamic neurons is complete. Satb2 specifies upper layer neurons (shown in red) in part by repressing deep-layer neuronal specifiers Ctip2 and Tbr1 [1, 4]. c RGPs integrate autocrine and paracrine factors originating from several sources including the meninges, vasculature, newborn neurons, and cerebrospinal fluid (CSF), many of which regulate RGP cell fate decisions