Expression of human-specific ARHGAP11B in mice leads to neocortex expansion and increased memory flexibility

EMBO J. 2021 Jul 1;40(13):e107093. doi: 10.15252/embj.2020107093. Epub 2021 May 3.


Neocortex expansion during human evolution provides a basis for our enhanced cognitive abilities. Yet, which genes implicated in neocortex expansion are actually responsible for higher cognitive abilities is unknown. The expression of human-specific ARHGAP11B in embryonic/foetal mouse, ferret and marmoset neocortex was previously found to promote basal progenitor proliferation, upper-layer neuron generation and neocortex expansion during development, features commonly thought to contribute to increased cognitive abilities. However, a key question is whether this phenotype persists into adulthood and if so, whether cognitive abilities are indeed increased. Here, we generated a transgenic mouse line with physiological ARHGAP11B expression that exhibits increased neocortical size and upper-layer neuron numbers persisting into adulthood. Adult ARHGAP11B-transgenic mice showed altered neurobehaviour, notably increased memory flexibility and a reduced anxiety level. Our data are consistent with the notion that neocortex expansion by ARHGAP11B, a gene implicated in human evolution, underlies some of the altered neurobehavioural features observed in the transgenic mice, such as the increased memory flexibility, a neocortex-associated trait, with implications for the increase in cognitive abilities during human evolution.

Keywords: basal progenitors; brain evolution; human-specific gene; memory flexibility; neocortex expansion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Biological Evolution
  • Cell Proliferation / physiology
  • Cognition / physiology
  • Female
  • GTPase-Activating Proteins / metabolism*
  • Humans
  • Male
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neocortex / metabolism*
  • Neocortex / physiology*
  • Neurogenesis / physiology
  • Neurons / metabolism*
  • Neurons / physiology*


  • ARHGAP11B protein, human
  • GTPase-Activating Proteins