Figure 3.

Molecules that control subtype-dependent cortical neuron integration. The migration and distribution along the radial and tangential axis are regulated by multiple ligand/receptor molecules expressed in neocortical subtypes. In deep layers, Ctip2-positive subcerebral projection neurons form periodic organizations in layer 5, observed in both the mouse and human neocortex. In humans, the expression segregation of NOS1 in these columns is regulated by FMRP. Upper-layer neurons require Cdk5 and ApoER2 for their migration. Within the upper-layers, Satb2-, and Unc5d-positive neurons represent distinct subpopulations. The latter exhibits delayed integration into the CP through repulsive interactions, with high FLRT2 expression at E15.5 that decreases perinatally. In turn, FLRT3 regulates the tangential dispersion of E15.5-born UL neurons through adhesive interactions. In turn, the radial distribution of Satb2-positive UL neurons is regulated by Robo1. Apart from these molecules, the tangential integration of neocortical neurons is regulated through multiple ephrin-As, which facilitate lateral dispersion of both DL and UL neurons. Ephrin-B1 reverse signaling, in turn, is required to limit the tangential dispersion of ontogenic columns derived from E13.5-born progenitor cells. MZ, marginal zone; SP, subplate.