This reduction in Tc, by means of a reduction in TG1 and to a lesser extent in TS (Figure 2I), is associated with an increase in proliferative divisions (Figure 2C) and a reduction of cell-cycle exit (Figure 2E), in agreement with the relationship between TG1 and the mode of division in cortical precursors (Pilaz et al., 2009). Combined, these two processes contribute to the expansion of the OSVZ precursor pool observed at midcorticogenesis (Figure 7C). Tc shortening and decrease in cell-cycle exit rates are observed simultaneously

in OSVZ and VZ. However, whereas the OSVZ continues to expand, the VZ declines, which suggests that the OSVZ expansion may benefit from a sustained or increased seeding by VZ precursors (LaMonica et al., 2013). The VZ starts to expand at early stages, before the generation of the OSVZ (Rakic, 2009). The observed coordination between Tc regulation in VZ and OSVZ at late stages underlies the important this website R428 concentration role of the VZ in cortical expansion throughout corticogenesis. Supragranular layer neurons are generated by the OSVZ (Lukaszewicz et al., 2005). Therefore, this expansion of the OSVZ pool via Tc shortening and decrease

in cell-cycle exit accounts for the sustained production of supragranular neurons during the second half of corticogenesis. This leads to the postulation that these specific properties of macaque OSVZ precursors account for the ADP ribosylation factor expansion of the cortex and the supragranular layer enlargement that characterize this species as well as the human. One can hypothesize that the fine regulation of the cell cycle, beyond its impact on the size of the progenitor pools, will also influence distinct transcriptional sequences in precursors that will in turn determine postmitotic transcriptional programs generating neuronal diversity (Molyneaux et al., 2007), as suggested by a recent study showing that the combinatorial temporal patterning of precursors is responsible for increasing diversity

in Drosophila CNS ( Bayraktar and Doe, 2013). In addition to their capacity to undergo symmetric proliferative divisions, as well as to self-renew, each of the five precursor types is able to generate neurons at E65 and E78. This indicates that OSVZ precursors generate neurons destined for infragranular and supragranular layers (Dehay et al., 1993 and Rakic, 1974). The lineage relationships between the different OSVZ precursor types revealed by the state transition diagrams provide a model of cortical development that departs from the prevailing view in which bRGs produce TAPs—identified as IPs—which symmetrically amplify before producing neurons (Figure 7B) (Fietz and Huttner, 2011, Fietz et al., 2010, Kriegstein et al., 2006 and Lui et al., 2011). We report frequencies of transitions at the total precursor population level (Figure 6E) as well as neurogenic transitions for individual precursor types (Figure 6C).