Sonic hedgehog signaling promotes basal radial glia and 1 intermediate progenitor cell

The unique mental abilities of humans are rooted in the immensely expanded and folded neocortex, which reflects the expansion of neural progenitors, especially basal progenitors including basalradial glia (bRGs, also called outer RGs) and intermediate progenitor cells (IPCs). Here, we show that constitutively active Shh signaling expanded basal progenitors and induced folding in the otherwise smooth mouse neocortex, whereas the loss of Shh signaling decreased the number of basal progenitors and the size of the neocortex. SHH signaling was strongly active in the human fetal neocortex but not in the mouse embryonic neocortex, and blocking SHH signaling in humancerebral organoids decreased the number of bRGs. Mechanistically, Shh signaling increased theinitial generation and self-renewal of bRGs as well as increasing IPC proliferation. Thus, robust SHH signaling in the human fetal neocortex may contribute to basal progenitor expansion and neocortical growth and folding. Overall design: 2 normal WT lateral cortical embrynonic E14.5 samples are compared to 3 medial samples in mouse