Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset

• Published in: Science (American Association for the Advancement of Science) 2020-07, Vol.369 (6503), p.546-550
• Main Authors: Heide, Michael, Haffner, Christiane, Murayama, Ayako, Kurotaki, Yoko, Shinohara, Haruka, Okano, Hideyuki, Sasaki, Erika, Huttner, Wieland B.
• Format: Article
• Language: English
• Subjects: Brain; Cerebral cortex; Evolution; Fetuses; Gene expression; Mammals; Neocortex; Primates
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abb2401

Along the path of human evolution, gene duplication and divergence produced a protein, ARHGAP11B, that is found in humans but not nonhuman primates or other mammals. Heide et al. analyzed the effects of ARHGAP11B gene expression, under control of its own human-specific promoter, in the fetal marmoset (see the Perspective by Dehay and Kennedy). In the early weeks of fetal growth, the gene drove greater elaboration of neural progenitors and neocortex than is evident in the normal fetal marmoset. ARHGAP11B expression may be one cause of the more robust neocortex that characterizes the human brain. Science , this issue p. 546 ; see also p. 506 Tests in marmosets solidify the link between a human-specific gene and the thicker brain neocortex characteristic of humans. The neocortex has expanded during mammalian evolution. Overexpression studies in developing mouse and ferret neocortex have implicated the human-specific gene ARHGAP11B in neocortical expansion, but the relevance for primate evolution has been unclear. Here, we provide functional evidence that ARHGAP11B causes expansion of the primate neocortex. ARHGAP11B expressed in fetal neocortex of the common marmoset under control of the gene’s own (human) promoter increased the numbers of basal radial glia progenitors in the marmoset outer subventricular zone, increased the numbers of upper-layer neurons, enlarged the neocortex, and induced its folding. Thus, the human-specific ARHGAP11B drives changes in development in the nonhuman primate marmoset that reflect the changes in evolution that characterize human neocortical development.