The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map

The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 Eomes Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism.

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Elsen GE, Hodge RD, Bedogni F, Daza RA, Nelson BR, Shiba N, Reiner SL, Hevner RF