ARHGAP11B (Rho GTPase Activating Protein 11B)

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ARHGAP11B is a partial duplication of the ARHFAP11A gene that arose after the human lineage diverged from the Pan genus but prior to the split with Neandertal and Denisovan. ARHGAPs are Rho guanosine triphosphatase–activating proteins activate Rho GTPases and are important in regulating a broad range of cellular signaling processes. ARHGAP11B contains most of the ARHGAP11A GAP-domain followed by a unique C-terminal sequence, however it is functionally distinct not displaying RhoA/Rho- kinase activity. Overexpression in mouse neocortex induces increased basal progenitor generation, thickening of the subventricular zone, and induction of cortical folding. These changes are cause by ARHGAP11B inducing basal progenitor cells to self-replicate. These findings make ARHGAP11B a likely candidate in the evolutionary expansion of the human neocortex.

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References

  1. Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development, Xing, Lei, Gkini Vasiliki, Nieminen Anni I., Zhou Hui-Chao, Aquilino Matilde, Naumann Ronald, Reppe Katrin, Tanaka Kohichi, Carmeliet Peter, Heikinheimo Oskari, et al. , Nature Communications, 2024/04/24, Volume 15, Issue 1, (2024)
  2. Neocortical neurogenesis in development and evolution—Human‐specific features, Huttner, Wieland B., Heide Michael, Mora‐Bermúdez Felipe, and Namba Takashi , Journal of Comparative Neurology, 2024/01/08, Volume 532, Issue 2, (2024)
  3. What Makes Us Human: Insights from the Evolution and Development of the Human Neocortex, Namba, Takashi, and Huttner Wieland B. , Annual Review of Cell and Developmental Biology, 2024/10/02, Volume 40, Issue 1, p.427-452, (2024)
  4. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion., Florio, Marta, Albert Mareike, Taverna Elena, Namba Takashi, Brandl Holger, Lewitus Eric, Haffner Christiane, Sykes Alex, Wong Fong Kuan, Peters Jula, et al. , Science, 2015 Mar 27, Volume 347, Issue 6229, p.1465-70, (2015)