Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion

Abstract

Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. In this work, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of ARHGAP11A (which encodes a Rho guanosine triphosphatase-activating protein) on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.

Dendritic spine actin cytoskeleton in autism spectrum disorder

“…Its genetic link to ASD and its presence in the brain during development suggest a potential role for ARHGAP11B in dendritic spine morphogenesis and plasticity, but this is still to be demonstrated 295,296 .…”

Human cerebral organoids recapitulate gene expression programs of fetal neocortex development

“…S1C), and we excluded these cells from further analyses. We next used all expressed genes to characterize cells based on their maximum correlation with bulk RNA-seq data from laser-dissected germinal zones, namely VZ (containing a majority of aRG), iSVZ and oSVZ (containing a majority of bIPs, bRG neurons, and migrating neurons), and CP (containing mature neurons) (18), or FACS-purified aRG, bRG, and neurons (19) (Fig. 1B).…”

Relaxed genetic control of cortical organization in human brains compared with chimpanzees

“…The fossil evidence demonstrates that these changes occurred in the hominin lineage over the last ∼6-8 My (4-9) in parallel with modifications to neurodevelopmental rates (10)(11)(12)(13). Although some of these changes have been linked to certain genetic variants in the human lineage [either shared with other late hominin species or exclusive to modern humans (14,15)], exploring brain evolution in hominins is challenging because of the limitations of the endocranial fossil record (4,5). Comparisons of chimpanzee and human brains therefore are essential to reveal the neural traits that differ between the two species, that underlie their behavioral specializations, and that must have evolved after they split from their last common ancestor.…”