Human-specific morphoregulatory signatures in basal radial glia characterize neocortex evolution

As the seat of our cognition, the human neocortex is an object of immense fascination. Human neocortex expansion during evolution has been attributed to an increase in the proliferative capacity of neural progenitor cells during development, particularly basal radial glia (bRG). Despite their evolutionary relevance, the genomic changes driving human-specific bRG biology remain uncharacterized. We used comparative chromatin and transcriptional profiling of neural progenitor cells isolated from gorilla, chimpanzee and human cerebral organoids to identify cis-regulatory elements that have gained activity in humans. Focusing specifically on bRG, we discovered that morphoregulatory enhancer activity and gene expression signatures distinguish human bRG from other great apes. Functional analysis of the morphoregulatory genes FAM107A and CNGA3 in human organoids revealed that these genes are required for the morphological complexity of human bRG. Taken together, our interspecies comparison of basal radial glia suggests that human-specific morphoregulatory signatures characterize neocortex evolution.