Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex

Abstract The evolutionary increase in size and complexity of the primate neocortex is thought to underlie the higher cognitive abilities of humans. ARHGAP11B is a human-specific gene that, based on its expression pattern in fetal human neocortex and progenitor effects in embryonic mouse neocortex, has been proposed to have a key function in the evolutionary expansion of the neocortex. Here, we study the effects of ARHGAP11B expression in the developing neocortex of the gyrencephalic ferret. In contrast to its effects in mouse, ARHGAP11B markedly increases proliferative basal radial glia, a progenitor cell type thought to be instrumental for neocortical expansion, and results in extension of the neurogenic period and an increase in upper-layer neurons. As a consequence, the postnatal ferret neocortex exhibits an increased neuron density in the upper cortical layers and expands in the radial dimension. Thus, human-specific ARHGAP11B can elicit hallmarks of neocortical expansion in developing ferret neocortex.