Figure 6.

Differential neuronal production from VZ precursor subtypes. The experiments in this study were conducted at mid-neurogenesis (E13.5–E14.5), the stage during which stellate and pyramidal neurons begin to be generated from precursors in the VZ and SVZ. Our data demonstrate that pGLAST⁺ RGCs and pTα1⁺ SNPs exhibit markedly different cell cycle kinetics and that SNPs persist in the VZ for at least two cell divisions (Fig. 2). The Cre/lox fate-mapping studies show that SNPs and RGCs present in the VZ at the same time produce different types of neurons, as defined by their laminar position (Fig. 4). Because of the inside-out nature of cortical layer formation, layer IV neurons are born before neurons residing in layer II/III. Furthermore, these experiments demonstrate that RGCs divide in the VZ to directly generate a small number of layer IV neurons and that they also indirectly generate layer II/III neurons via IPC divisions in the SVZ. These IPC divisions take additional time; thus, progeny of the RGC antecedents are spread radially over a large laminar area. In contrast, SNPs within the E14.5 VZ do not generate appreciable numbers of INPs but rather generate neuronal progeny directly from the VZ, which are allocated more quickly and specifically to layer IV. Thus, RGCs contribute more substantially to laminar expansion by producing neurons for multiple layers over a longer period of time, whereas SNPs generate discrete neuronal populations over a short time window.