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Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion
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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In the citing paper
“A subsequent point mutation introduced a novel splice donor site, resulting in a new coding exon and a truncated protein with distinct functional properties.”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
In the citing paper
“It is predominantly expressed in basal progenitor cells within the developing human neocortex.”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
In the citing paper
“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.”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
In the citing paper
“These findings suggest that ARHGAP11B played a pivotal role in the evolutionary expansion and increased complexity of the human neocortex [54].”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
In the citing paper
“ARHGAP11B is a human-specific gene that originated approximately 5 million years ago through a partial duplication of the ancestral gene ARHGAP11A.”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
In the citing paper
“Its expression promotes the proliferation of these progenitors, leading to an increased pool of neurons and contributing to the expansion of the neocortical surface area—a hallmark of the human brain.”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
In the citing paper
“For instance, introducing ARHGAP11B into murine neuronal progenitors using gene editing or overexpression systems induced an expansion similar to that observed in the human cortex, suggesting a causal role in cognitive enhancement [54].”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
In the citing paper
“Of the genes that were preferentially expressed in human RG cells compared to iPCs and neurons, 56 lacked a mouse ortholog.”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Florio et al., 2015
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Mechanics in the nervous system: From development to disease
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Epigenome profiling and editing of neocortical progenitor cells during development
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Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins
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Human evolution: the non-coding revolution
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Metadata
- 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
- ORCID
- 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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