Cited by 634Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationGenetics and Neurodevelopmental Disorders

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 +12 more·2015·Science

Abstract

Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. In this work, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of ARHGAP11A (which encodes a Rho guanosine triphosphatase-activating protein) on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.

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Crossref · 10.1126/science.aaa1975

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  • A subsequent point mutation introduced a novel splice donor site, resulting in a new coding exon and a truncated protein with distinct functional properties.

    “A subsequent point mutation introduced a novel splice donor site, resulting in a new coding exon and a truncated protein with distinct functional properties.”
  • ARHGAP11B is predominantly expressed in basal progenitor cells within the developing human neocortex.

    “It is predominantly expressed in basal progenitor cells within the developing human neocortex.”
  • Ectopic expression of ARHGAP11B in the embryonic mouse neocortex increases the number of basal progenitors and induces cortical folding (gyrification), a feature absent in the lissencephalic mouse brain.

    “Ectopic expression of ARHGAP11B in the embryonic mouse neocortex has been shown to increase the number of basal progenitors and induce cortical folding (gyrification), a feature absent in the lissencephalic (smooth) mouse brain.”
  • ARHGAP11B played a pivotal role in the evolutionary expansion and increased complexity of the human neocortex.

    “These findings suggest that ARHGAP11B played a pivotal role in the evolutionary expansion and increased complexity of the human neocortex [54].”
  • ARHGAP11B is a human-specific gene that originated approximately 5 million years ago through a partial duplication of the ancestral gene ARHGAP11A.

    “ARHGAP11B is a human-specific gene that originated approximately 5 million years ago through a partial duplication of the ancestral gene ARHGAP11A.”

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Authors
Florio, M., Albert, M., Taverna, E., Namba, T., Brandl, H., Lewitus, E., Haffner, C., Sykes, A., Wong, F. K., Peters, J., Guhr, E., Klemroth, S., Prüfer, K., Kelso, J., Naumann, R., Nüsslein, I., Dahl, A., Lachmann, R., Pääbo, S., & Huttner, W. B.
Affiliations
  • Max Planck Institute of Molecular Cell Biology and Genetics (DE)
  • Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Pfotenhauerstraße 108, D-01307 Dresden, Germany.
  • Center for Regenerative Therapies Dresden (DE)
  • Max Planck Institute for Evolutionary Anthropology (DE)
  • University Hospital Carl Gustav Carus (DE)
Corresponding author
  • Albert, Mareike
  • Taverna, Elena
  • Namba, Takashi
Venue
Science
Published
2015-03-27
Volume
347
Issue
6229
Pages
1465-1470
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1985911270
Cited by
632
References
42
Citations by year
2026: 43 · 2025: 50 · 2024: 58 · 2023: 65 · 2022: 52 · 2021: 69 · 2020: 70 · 2019: 56 · 2018: 40 · 2017: 43 · 2016: 59 · 2015: 27
FWCI
22.77
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • European Research Council (250197)
  • Deutsche Forschungsgemeinschaft (SFB 655)
  • Fonds der Chemischen Industrie
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
ARHGAP11A, neocortex expansion, human brain evolution, radial glia, subventricular zone, cortical plate, cortical folding, gene duplication, RhoGAP, transcriptome, cell polarity, mouse neocortex
MeSH terms
Animals, Cell Separation, Humans, Neuroglia, Neurons, Protein Structure, Tertiary, Gene Expression Regulation, Developmental, Neocortex, Gene Duplication, Lateral Ventricles, GTPase-Activating Proteins, Mice, Neurogenesis, Neural Stem Cells, Transcriptome

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