Extracellular matrix-inducing Sox9 orchestrates basal progenitor proliferation and gliogenesis in developing neocortex

Neocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. Examination of Sox9 expression reveals that Sox9 is expressed in BPs of developing ferret and human, but not mouse neocortex. Functional studies by conditional Sox9 expression in the mouse BP lineage demonstrate increased BP proliferation, reduced Tbr2 and induction of Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell non-autonomous stimulation of BP proliferation followed by increased production of upper-layer neurons. Collectively, our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic as well as gliogenic BP cell fate, suggesting that Sox9 acts a master regulator in the subventricular zone to promote neocortical expansion. Overall design: Comparison of transcriptomes and analysis of differentially expressed genes in embryonic mouse basal progenitors, electroporated with either control construct (referred as control) or with a conditional Sox9 expression construct (referred as Sox9). Control had 3 replicates, Sox9 had 4 replicates.