Human-specificARHGAP11Bis necessary and sufficient for human-type basal progenitor levels in primate brain organoids

Based on studies in various animal models, including developing ferret neocortex (Kalebic et al., 2018), the human-specific geneARHGAP11Bhas been implicated in human neocortex expansion. However, the extent of its contribution to this expansion during primate evolution is unknown. Here we addressed this issue by genetic manipulation of ARHGAP11B levels and function in chimpanzee and human cerebral organoids. Interference with ARHGAP11B’s function in human cerebral organoids caused a massive decrease, down to a chimpanzee level, in the proliferation and abundance of basal progenitors, the progenitors thought to have a key role in neocortex expansion. Conversely,ARHGAP11Bexpression in chimpanzee cerebral organoids resulted in a doubling of cycling basal progenitors. Taken together, our findings demonstrate thatARHGAP11Bis necessary and sufficient to maintain the elevated basal progenitor levels that characterize the fetal human neocortex, suggesting that this human-specific gene was a major contributor to neocortex expansion during human evolution.