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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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.”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
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.”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
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.”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
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].”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [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.”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [54]
ARHGAP11B expression promotes the proliferation of basal progenitors, leading to an increased pool of neurons and contributing to the expansion of the neocortical surface area.
“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]
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.
“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]
Of genes preferentially expressed in human radial glia cells compared to intermediate progenitor cells and neurons, 56 lacked a mouse ortholog.
“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
Cites
Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase)
Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., et al. (1996) · Science · doi:10.1126/science.273.5272.245 · Cited by 2,889 · see citing works
The complete genome sequence of a Neanderthal from the Altai Mountains
Prüfer, K., Racimo, F., Patterson, N., Jay, F., Sankararaman, S., Sawyer, S., Heinze, A., Renaud, G., Sudmant, P. H., de Filippo, C., et al. (2014) · Nature · doi:10.1038/nature12886 · Cited by 2,254 · see citing works
A high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967 · see citing works
Evolution of the neocortex: a perspective from developmental biology
Rakic, P. (2009) · Nature reviews. Neuroscience · doi:10.1038/nrn2719 · Cited by 1,565 · see citing works
Development and Evolution of the Human Neocortex
Lui, J. H., Hansen, D. V., & Kriegstein, A. R. (2011) · Cell · doi:10.1016/j.cell.2011.06.030 · Cited by 1,342 · see citing works
Transcriptional landscape of the prenatal human brain
Miller, J. A., Ding, S.-L., Sunkin, S. M., Smith, K. A., Ng, L., Szafer, A., Ebbert, A., Riley, Z. L., Royall, J. J., Aiona, K., et al. (2014) · Nature · doi:10.1038/nature13185 · Cited by 1,325 · see citing works
Englund, C., Fink, A., Lau, C., Pham, D., Daza, R. A. M., Bulfone, A., Kowalczyk, T., & Hevner, R. F. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2899-04.2005 · Cited by 1,261 · see citing works
Haubensak, W. E., Attardo, A., Denk, W. T., & Huttner, W. Β. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308600100 · Cited by 1,004 · see citing works
Pollen, A. A., Nowakowski, T. J., Shuga, J., Wang, X., Leyrat, A. A., Lui, J. H., Li, N., Szpankowski, L., Fowler, B., Chen, P., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2967 · Cited by 920 · see citing works
Taverna, E., Götz, M., & Huttner, W. Β. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155801 · Cited by 737 · see citing works
Smart, I. H. M. (2002) · Cerebral Cortex · doi:10.1093/cercor/12.1.37 · Cited by 687 · see citing works
Diversity of Human Copy Number Variation and Multicopy Genes
Sudmant, P. H., Kitzman, J. O., Antonacci, F., Alkan, C., Malig, M., Tsalenko, A., Sampas, N., Bruhn, L., Shendure, J., 1000 Genomes Project, et al. (2010) · Science · doi:10.1126/science.1197005 · Cited by 667 · see citing works
Neural progenitors, neurogenesis and the evolution of the neocortex
Florio, M., & Huttner, W. Β. (2014) · Development · doi:10.1242/dev.090571 · Cited by 624 · see citing works
A new subtype of progenitor cell in the mouse embryonic neocortex
Wang, X., Tsai, J.-W., LaMonica, B., & Kriegstein, A. R. (2011) · Nature Neuroscience · doi:10.1038/nn.2807 · Cited by 507 · see citing works
Growth and folding of the mammalian cerebral cortex: from molecules to malformations
Sun, T., & Hevner, R. F. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3707 · Cited by 471 · see citing works
Betizeau, M., Cortay, V., Patti, D., Pfister, S., Gautier, E., Bellemin-Ménard, A., Afanassieff, M., Huissoud, C., Douglas, R. J., Kennedy, H., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.032 · Cited by 462 · see citing works
Neural stem and progenitor cells shorten S-phase on commitment to neuron production
Arai, Y., Pulvers, J. N., Haffner, C., Schilling, B., Nüsslein, I., Calegari, F., & Huttner, W. Β. (2011) · Nature Communications · doi:10.1038/ncomms1155 · Cited by 372 · see citing works
Fietz, S. A., Lachmann, R., Brandl, H., Kircher, M., Samusik, N., Schröder, R., Lakshmanaperumal, N., Henry, I., Vogt, J., Riehn, A., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209647109 · Cited by 337 · see citing works
Paridaen, J. T. M. L., Wilsch‐Bräuninger, M., & Huttner, W. Β. (2013) · Cell · doi:10.1016/j.cell.2013.08.060 · Cited by 318 · see citing works
G1 Phase Regulation, Area-Specific Cell Cycle Control, and Cytoarchitectonics in the Primate Cortex
Lukaszewicz, A., Savatier, P., Cortay, V., Giroud, P., Huissoud, C., Berland, M., Kennedy, H., & Dehay, C. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.032 · Cited by 315 · see citing works
Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex
Johnson, M. B., Wang, P. P., Atabay, K. D., Murphy, E. A., Doan, R. N., Hecht, J. L., & Walsh, C. A. (2015) · Nature Neuroscience · doi:10.1038/nn.3980 · Cited by 288 · see citing works
Cortical progenitor expansion, self-renewal and neurogenesis—a polarized perspective
Fietz, S. A., & Huttner, W. Β. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.10.002 · Cited by 270 · see citing works
Stahl, R., Walcher, T., Romero, C. D. J., Pilz, G.-A., Cappello, S., Irmler, M., Sanz-Aquela, J. M., Beckers, J., Blum, R., Borrell, V., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.027 · Cited by 267 · see citing works
Role of radial glial cells in cerebral cortex folding
Borrell, V., & Götz, M. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.02.007 · Cited by 221 · see citing works
Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis
Kawaguchi, A., Ikawa, T., Kasukawa, T., Ueda, H. R., Kurimoto, K., Saitou, M., & Matsuzaki, F. (2008) · Development · doi:10.1242/dev.022616 · Cited by 193 · see citing works
Emerging roles of neural stem cells in cerebral cortex development and evolution
Borrell, V., & Reillo, I. (2012) · Developmental Neurobiology · doi:10.1002/dneu.22013 · Cited by 185 · see citing works
Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex
Lui, J. H., Nowakowski, T. J., Pollen, A. A., Javaherian, A., Kriegstein, A. R., & Oldham, M. C. (2014) · Nature · doi:10.1038/nature13973 · Cited by 166 · see citing works
Attardo, A., Calegari, F., Haubensak, W. E., Wilsch‐Bräuninger, M., & Huttner, W. Β. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002388 · Cited by 165 · see citing works
Myosin II is required for interkinetic nuclear migration of neural progenitors
Schenk, J., Wilsch‐Bräuninger, M., Calegari, F., & Huttner, W. Β. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908928106 · Cited by 163 · see citing works
Bian, S., Hong, J., Li, Q., Schebelle, L., Pollock, A., Knauss, J. L., Garg, V., & Sun, T. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.03.037 · Cited by 163 · see citing works
An Adaptive Threshold in Mammalian Neocortical Evolution
Lewitus, É., Kelava, I., Kalinka, A. T., Tomančák, P., & Huttner, W. Β. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1002000 · Cited by 162 · see citing works
Antonacci, F., Dennis, M. Y., Huddleston, J., Sudmant, P. H., Steinberg, K. M., Rosenfeld, J. A., Miroballo, M., Graves, T., Vives, L., Malig, M., et al. (2014) · Nature Genetics · doi:10.1038/ng.3120 · Cited by 144 · see citing works
Ayoub, A. E., Oh, S., Xie, Y., Leng, J., Cotney, J., Dominguez, M. H., Noonan, J. P., & Rakic, P. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112213108 · Cited by 129 · see citing works
Riley, B. P., Williamson, M. P., Collier, D. A., Wilkie, H., & MAKOFF, A. J. (2002) · Genomics · doi:10.1006/geno.2002.6694 · Cited by 115 · see citing works
Promotion of embryonic cortico-cerebral neuronogenesis by miR-124
Maiorano, N. A., & Mallamaci, A. (2009) · Neural Development · doi:10.1186/1749-8104-4-40 · Cited by 110 · see citing works
Zanin, E., Desai, A. B., Poser, I., Toyoda, Y., Andree, C., Moebius, C., Bickle, M., Conradt, B., Piekny, A. J., & Oegema, K. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.08.005 · Cited by 105 · see citing works
Cortical Gyrification Induced by Fibroblast Growth Factor 2 in the Mouse Brain
Rash, B. G., Tomasi, S., Lim, H., Suh, C. Y., & Vaccarino, F. M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3621-12.2013 · Cited by 103 · see citing works
MicroRNA-92b regulates the development of intermediate cortical progenitors in embryonic mouse brain
Nowakowski, T. J., Fotaki, V., Pollock, A., Sun, T., Pratt, T., & Price, D. J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219385110 · Cited by 91 · see citing works
Kagawa, Y., Matsumoto, S., Kamioka, Y., Mimori, K., Naito, Y., Ishii, T., Okuzaki, D., Nishida, N., Maeda, S., Naito, A., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083629 · Cited by 87 · see citing works
Arcila, M. L., Betizeau, M., Cambronne, X. A., Guzman, E., Doerflinger, N., Bouhallier, F., Zhou, H., Wu, B., Rani, N., Bassett, D. S., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.017 · Cited by 80 · see citing works
Houlihan, S. L., & Feng, Y. (2014) · eLife · doi:10.7554/elife.03297 · Cited by 49 · see citing works
A new approach to manipulate the fate of single neural stem cells in tissue
Taverna, E., Haffner, C., Pepperkok, R., & Huttner, W. Β. (2011) · Nature Neuroscience · doi:10.1038/nn.3008 · Cited by 36 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Human cerebral organoids recapitulate gene expression programs of fetal neocortex development
Camp, J. G., Badsha, F., Florio, M., Kanton, S., Gerber, T., Wilsch-Bräuninger, M., Lewitus, E., Sykes, A., Hevers, W., Lancaster, M., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520760112 · Cited by 1,130 · see citing works
Molecular Identity of Human Outer Radial Glia during Cortical Development
Pollen, A. A., Nowakowski, T. J., Chen, J., Retallack, H., Sandoval-Espinosa, C., Nicholas, C. R., Shuga, J., Liu, S. J., Oldham, M. C., Diaz, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.004 · Cited by 908 · see citing works
Integrative functional genomic analysis of human brain development and neuropsychiatric risks
Li, M., Santpere, G., Imamura Kawasawa, Y., Evgrafov, O. V., Gulden, F. O., Pochareddy, S., Sunkin, S. M., Li, Z., Shin, Y., Zhu, Y., et al. (2018) · Science · doi:10.1126/science.aat7615 · Cited by 810 · see citing works
The Cellular and Molecular Landscapes of the Developing Human Central Nervous System
Silbereis, J. C., Pochareddy, S., Zhu, Y., Li, M., & Sestan, N. (2016) · Neuron · doi:10.1016/j.neuron.2015.12.008 · Cited by 818 · see citing works
A high-coverage Neandertal genome from Vindija Cave in Croatia
Prüfer, K., de Filippo, C., Grote, S., Mafessoni, F., Korlević, P., Hajdinjak, M., Vernot, B., Skov, L., Hsieh, P., Peyrégne, S., et al. (2017) · Science · doi:10.1126/science.aao1887 · Cited by 719 · see citing works
Organoid single-cell genomic atlas uncovers human-specific features of brain development
Kanton, S., Boyle, M. J., He, Z., Santel, M., Weigert, A., Sanchís-Calleja, F., Guijarro, P., Sidow, L., Fleck, J. S., Han, D., et al. (2019) · Nature · doi:10.1038/s41586-019-1654-9 · Cited by 761 · see citing works
Brain organoids: advances, applications and challenges
Qian, X., Song, H., & Ming, G.-L. (2019) · Development · doi:10.1242/dev.166074 · Cited by 724 · see citing works
Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis
Fiddes, I. T., Lodewijk, G. A., Mooring, M., Bosworth, C. M., Ewing, A. D., Mantalas, G. L., Novak, A. M., van den Bout, A., Bishara, A., Rosenkrantz, J. L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.051 · Cited by 595 · see citing works
Chromosome conformation elucidates regulatory relationships in developing human brain
Won, H., de la Torre-Ubieta, L., Stein, J. L., Parikshak, N. N., Huang, J., Opland, C. K., Gandal, M. J., Sutton, G. J., Hormozdiari, F., Lu, D., et al. (2016) · Nature · doi:10.1038/nature19847 · Cited by 584 · see citing works
Evolution of the Human Nervous System Function, Structure, and Development
Sousa, A. M. M., Meyer, K. A., Santpere, G., Gulden, F. O., & Sestan, N. (2017) · Cell · doi:10.1016/j.cell.2017.06.036 · Cited by 517 · see citing works
Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta/Notch Regulation
Suzuki, I. K., Gacquer, D., Van Heurck, R., Kumar, D., Wojno, M., Bilheu, A., Herpoel, A., Lambert, N., Cheron, J., Polleux, F., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.067 · Cited by 471 · see citing works
Induction of Expansion and Folding in Human Cerebral Organoids
Li, Y., Muffat, J., Omer, A., Bosch, I., Lancaster, M. A., Sur, M., Gehrke, L., Knoblich, J. A., & Jaenisch, R. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.11.017 · Cited by 436 · see citing works
Human brain organoids on a chip reveal the physics of folding
Karzbrun, E., Kshirsagar, A., Cohen, S., Hanna, J. H., & Reiner, O. (2018) · Nature Physics · doi:10.1038/s41567-018-0046-7 · Cited by 421 · see citing works
New insights into the development of the human cerebral cortex
Molnár, Z., Clowry, G. J., Šestan, N., Alzu’bi, A., Bakken, T. E., Hevner, R. F., Hüppi, P. S., Kostović, I., RAKIC, P. T., Anton, E. S., et al. (2019) · Journal of Anatomy · doi:10.1111/joa.13055 · Cited by 401 · see citing works
Proliferation control in neural stem and progenitor cells
Homem, C. C. F., Repic, M., & Knoblich, J. A. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn4021 · Cited by 377 · see citing works
Innovations present in the primate interneuron repertoire
Krienen, F. M., Goldman, M., Zhang, Q., C. H. del Rosario, R., Florio, M., Machold, R., Saunders, A., Levandowski, K., Zaniewski, H., Schuman, B., et al. (2020) · Nature · doi:10.1038/s41586-020-2781-z · Cited by 381 · see citing works
Self-citationStem Cell Models of Human Brain Development
Kelava, I., & Lancaster, M. A. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.05.022 · Cited by 371 · see citing works
Innovations in Primate Interneuron Repertoire
Krienen, F. M., Goldman, M., Zhang, Q., del Rosario, R., Florio, M., Machold, R., Saunders, A., Levandowski, K., Zaniewski, H., Schuman, B., et al. (2019) · doi:10.1101/709501 · Cited by 372 · see citing works
Self-citationFrom cohorts to molecules: adverse impacts of endocrine disrupting mixtures
Caporale, N., Leemans, M., Birgersson, L., Germain, P.-L., Cheroni, C., Borbély, G., Engdahl, E., Lindh, C., Bressan, R. B., Cavallo, F., et al. (2022) · Science · doi:10.1126/science.abe8244 · Cited by 368 · see citing works
Cerebral cortex expansion and folding: what have we learned?
Fernández, V., Llinares-Benadero, C., & Borrell, V. (2016) · The EMBO Journal · doi:10.15252/embj.201593701 · Cited by 357 · see citing works
High-resolution comparative analysis of great ape genomes
Kronenberg, Z. N., Fiddes, I. T., Gordon, D., Murali, S., Cantsilieris, S., Meyerson, O. S., Underwood, J. G., Nelson, B. J., Chaisson, M. J. P., Dougherty, M. L., et al. (2018) · Science · doi:10.1126/science.aar6343 · Cited by 350 · see citing works
Nowakowski, T. J., Pollen, A. A., Sandoval-Espinosa, C., & Kriegstein, A. R. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.005 · Cited by 347 · see citing works
Genetic variation and the de novo assembly of human genomes
Chaisson, M., Wilson, R. K., & Eichler, E. E. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3933 · Cited by 337 · see citing works
Richards, L. M., Whitley, O., MacLeod, G. D. A. H., Cavalli, F. M. G., Coutinho, F. J., Jaramillo, J. E., Svergun, N., Riverin, M., Croucher, D. C., Kushida, M. M., et al. (2021) · Nature Cancer · doi:10.1038/s43018-020-00154-9 · Cited by 316 · see citing works
Human cerebral organoids — a new tool for clinical neurology research
Eichmüller, O. L., & Knoblich, J. A. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00723-9 · Cited by 303 · see citing works
Mora‐Bermúdez, F., Badsha, F., Kanton, S., Camp, J. G., Vernot, B., Köhler, K., Voigt, B., Okita, K., Maričić, T., He, Z., et al. (2016) · eLife · doi:10.7554/elife.18683 · Cited by 294 · see citing works
The influence of evolutionary history on human health and disease
Benton, M. L., Abraham, A., LaBella, A. L., Abbot, P., Rokas, A., & Capra, J. A. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00305-9 · Cited by 291 · see citing works
Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex
Johnson, M. B., Wang, P. P., Atabay, K. D., Murphy, E. A., Doan, R. N., Hecht, J. L., & Walsh, C. A. (2015) · Nature Neuroscience · doi:10.1038/nn.3980 · Cited by 288 · see citing works
An early cell shape transition drives evolutionary expansion of the human forebrain
Benito-Kwiecinski, S. K., Giandomenico, S. L., Sutcliffe, M. A., Riis, E. S., Freire-Pritchett, P., Kelava, I., Wunderlich, S., Martin, U., Wray, G. A., McDole, K., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.050 · Cited by 275 · see citing works
How the extracellular matrix shapes neural development
Long, K. R., & Huttner, W. Β. (2019) · Open Biology · doi:10.1098/rsob.180216 · Cited by 270 · see citing works
Deconstructing cortical folding: genetic, cellular and mechanical determinants
Llinares-Benadero, C., & Borrell, V. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0112-2 · Cited by 243 · see citing works
Human brain organogenesis: Toward a cellular understanding of development and disease
Kelley, K. W., & Pașca, S. P. (2021) · Cell · doi:10.1016/j.cell.2021.10.003 · Cited by 233 · see citing works
Relaxed genetic control of cortical organization in human brains compared with chimpanzees
Gómez‐Robles, A., Hopkins, W. D., Schapiro, S. J., & Sherwood, C. C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1512646112 · Cited by 230 · see citing works
Fixed single-cell transcriptomic characterization of human radial glial diversity
Thomsen, E. R., Mich, J. K., Yao, Z., Hodge, R. D., Doyle, A. M., Jang, S., Shehata, S. I., Nelson, A. M., Shapovalova, N. V., Levi, B. P., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3629 · Cited by 227 · see citing works
Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals
Pinson, A., Xing, L., Namba, T., Kalebic, N., Peters, J., Oegema, C. E., Traikov, S., Reppe, K., Riesenberg, S., Maričić, T., et al. (2022) · Science · doi:10.1126/science.abl6422 · Cited by 228 · see citing works
Linaro, D., Vermaercke, B., Iwata, R., Ramaswamy, A., Davis, B. A., Boubakar, L., Libé-Philippot, B., Bilheu, A., Bruyne, L. D., Gall, D., et al. (2019) · doi:10.1101/626218 · Cited by 210 · see citing works
“While there has been major progress in understanding the mechanisms underlying the increase in human cortical size (Borrell and Gotz, 2014; Florio et al., 2015; Hansen et al., 2010; Stahl et al., 2013; Suzuki et al., 2018), this only explains a part of our brain evolution: features that are thought…”
BackgroundFlorio, M., Heide, M., Pinson, A., Brandl, H., Albert, M., Winkler, S., Wimberger, P., Huttner, W. Β., & Hiller, M. (2018) · eLife · doi:10.7554/elife.32332 · Cited by 201 · see citing works
Cellular and molecular introduction to brain development
Jiang, X., & Nardelli, J. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.07.007 · Cited by 199 · see citing works
Long, K. R., Newland, B., Florio, M., Kalebic, N., Langen, B., Kolterer, A., Wimberger, P., & Huttner, W. B. (2018) · Neuron · doi:10.1016/j.neuron.2018.07.013 · Cited by 196 · see citing works
Hedgehog signaling promotes basal progenitor expansion and the growth and folding of the neocortex
Wang, L., Hou, S., & Han, Y.-G. (2016) · Nature Neuroscience · doi:10.1038/nn.4307 · Cited by 190 · see citing works
Human Models Are Needed for Studying Human Neurodevelopmental Disorders
Zhao, X., & Bhattacharyya, A. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.10.009 · Cited by 192 · see citing works
The evolution and population diversity of human-specific segmental duplications
Dennis, M. Y., Harshman, L., Nelson, B. J., Penn, O., Cantsilieris, S., Huddleston, J., Antonacci, F., Penewit, K., Denman, L., Raja, A., et al. (2017) · Nature Ecology & Evolution · doi:10.1038/s41559-016-0069 · Cited by 159 · see citing works
Human adaptation and evolution by segmental duplication
Dennis, M. Y., & Eichler, E. E. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.08.001 · Cited by 189 · see citing works
Li, J., Pan, L., Pembroke, W. G., Rexach, J. E., Godoy, M. I., Condro, M. C., Alvarado, A. G., Harteni, M., Chen, Y., Stiles, L., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24232-3 · Cited by 187 · see citing works
Evolution of Cortical Neurogenesis in Amniotes Controlled by Robo Signaling Levels
Cárdenas, A., Villalba, A., Romero, C. D. J., Picó, E., Kyrousi, C., Tzika, A. C., Tessier‐Lavigne, M., Ma, L., Drukker, M., Cappello, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.007 · Cited by 188 · see citing works
Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset
Heide, M., Haffner, C., Murayama, A. Y., Kurotaki, Y., Shinohara, H., Okano, H., Sasaki, E., & Huttner, W. Β. (2020) · Science · doi:10.1126/science.abb2401 · Cited by 187 · see citing works
Regulation of cell-type-specific transcriptomes by microRNA networks during human brain development
Nowakowski, T. J., Rani, N., Golkaram, M., Zhou, H. R., Alvarado, B., Huch, K., West, J. A., Leyrat, A., Pollen, A. A., Kriegstein, A. R., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0265-3 · Cited by 166 · see citing works
Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly
Romero, C. D. J., Bruder, C. E. G., Tomasello, U., Sanz‐Anquela, J. M., & Borrell, V. (2015) · The EMBO Journal · doi:10.15252/embj.201591176 · Cited by 173 · see citing works
Primary Cilia in Brain Development and Diseases
Youn, Y. H., & Han, Y.-G. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2017.08.031 · Cited by 173 · see citing works
Developmental mechanisms underlying the evolution of human cortical circuits
Vanderhaeghen, P., & Polleux, F. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00675-z · Cited by 173 · see citing works
Ju, X.-C., Hou, Q.-Q., Sheng, A.-L., Wu, K.-Y., Zhou, Y., Jin, Y., Wen, T., Yang, Z., Wang, X., & Luo, Z. (2016) · eLife · doi:10.7554/elife.18197 · Cited by 169 · see citing works
Genetics of human brain development
Zhou, Y. F., Song, H., & Ming, G. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00626-5 · Cited by 173 · see citing works
Panksepp, J., Lane, R. D., Solms, M., & Smith, R. S. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.09.010 · Cited by 167 · see citing works
Jurisch‐Yaksi, N., Yaksi, E., & Kızıl, Ç. (2020) · Glia · doi:10.1002/glia.23849 · Cited by 155 · see citing works
Toward a conceptual framework for early brain and behavior development in autism
Piven, J., Elison, J. T., & Zylka, M. J. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.131 · Cited by 163 · see citing works
Kalebic, N., Gilardi, C., Stepien, B. K., Wilsch‐Bräuninger, M., Long, K. R., Namba, T., Florio, M., Langen, B., Lombardot, B., Shevchenko, A., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.02.017 · Cited by 161 · see citing works
Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis
Namba, T., Dóczi, J., Pinson, A., Xing, L., Kalebic, N., Wilsch‐Bräuninger, M., Long, K. R., Vaid, S., Lauer, J. L., Bogdanova, A. I., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.11.027 · Cited by 157 · see citing works
Human-specific genetics: new tools to explore the molecular and cellular basis of human evolution
Pollen, A. A., Kilik, U., Lowe, C. B., & Camp, J. G. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-022-00568-4 · Cited by 157 · see citing works
Brain evolution by brain pathway duplication
Chakraborty, M., & Jarvis, E. D. (2015) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0056 · Cited by 150 · see citing works
Modelling human brain development and disease with organoids
Birtele, M., Lancaster, M. A., & Quadrato, G. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00804-1 · Cited by 161 · see citing works
Rayón, T., Maizels, R. J., Barrington, C., & Briscoe, J. (2021) · Development · doi:10.1242/dev.199711 · Cited by 143 · see citing works
Liu, J., Liu, W., Yang, L., Wu, Q., Zhang, H., Fang, A., Li, L., Xu, X., Sun, L., Zhang, J., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.08.013 · Cited by 138 · see citing works
Selected Principles of Pankseppian Affective Neuroscience
Davis, K. L., & Montag, C. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.01025 · Cited by 145 · see citing works
Mapping gene regulatory circuitry of Pax6 during neurogenesis
Thakurela, S., Tiwari, N., Schick, S., Garding, A., Ivánek, R., Berninger, B., & Tiwari, V. K. (2016) · Cell Discovery · doi:10.1038/celldisc.2015.45 · Cited by 131 · see citing works
Regulation of Cerebral Cortex Folding by Controlling Neuronal Migration via FLRT Adhesion Molecules
del Toro, D., Ruff, T., Cederfjäll, E. A., Villalba, A., Seyit-Bremer, G., Borrell, V., & Klein, R. (2017) · Cell · doi:10.1016/j.cell.2017.04.012 · Cited by 138 · see citing works
How Cells Fold the Cerebral Cortex
Borrell, V. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1106-17.2017 · Cited by 139 · see citing works
Zeng, B., Liu, Z., Lu, Y., Zhong, S., Qin, S., Huang, L., Zeng, Y., Li, Z., Dong, H., Shi, Y., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.04.016 · Cited by 133 · see citing works
Mechanisms of radial glia progenitor cell lineage progression
Beattie, R., & Hippenmeyer, S. (2017) · FEBS Letters · doi:10.1002/1873-3468.12906 · Cited by 127 · see citing works
Buchsbaum, I. Y., & Cappello, S. (2019) · Development · doi:10.1242/dev.163766 · Cited by 128 · see citing works
Structural Basis of Teneurin-Latrophilin Interaction in Repulsive Guidance of Migrating Neurons
del Toro, D., Carrasquero, M., Chu, A., Ruff, T., Shahin, M., Jackson, V. A., Chavent, M. G., Berbeira-Santana, M., Seyit-Bremer, G., Brignani, S., et al. (2020) · Cell · doi:10.1016/j.cell.2019.12.014 · Cited by 130 · see citing works
A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development
Yao, Z., Mich, J. K., Ku, S., Menon, V., Krostag, A.-R., Martinez, R. A., Furchtgott, L., Mulholland, H., Bort, S. J., Fuqua, M. A., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.09.011 · Cited by 127 · see citing works
A 2020 view of tension-based cortical morphogenesis
Essen, D. C. V. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016830117 · Cited by 128 · see citing works
Genetics and mechanisms leading to human cortical malformations
Romero, D. M., Bahi‐Buisson, N., & Francis, F. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.09.031 · Cited by 126 · see citing works
Brain evolution and development: adaptation, allometry and constraint
Montgomery, S. H., Mundy, N. I., & Barton, R. A. (2016) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2016.0433 · Cited by 124 · see citing works
Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex
Kalebic, N., Gilardi, C., Albert, M., Namba, T., Long, K. R., Kostic, M., Langen, B., & Huttner, W. Β. (2018) · eLife · doi:10.7554/elife.41241 · Cited by 129 · see citing works
Sequential regulatory loops as key gatekeepers for neuronal reprogramming in human cells
Xue, Y., Qian, H., Hu, J., Zhou, B., Zhou, Y., Hu, X., Karakhanyan, A., Pang, Z., & Fu, X.-D. (2016) · Nature Neuroscience · doi:10.1038/nn.4297 · Cited by 118 · see citing works
Namba, T., & Huttner, W. Β. (2016) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.256 · Cited by 115 · see citing works
Mechanics in the nervous system: From development to disease
Pillai, E. K., & Franze, K. (2023) · Neuron · doi:10.1016/j.neuron.2023.10.005 · Cited by 116 · see citing works
Evolution of central neural circuits: state of the art and perspectives
Roberts, R. J. V., Pop, S., & Prieto-Godino, L. L. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00644-y · Cited by 108 · see citing works
Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells
Suzuki, I. K., & Vanderhaeghen, P. (2015) · Development · doi:10.1242/dev.120568 · Cited by 110 · see citing works
Epigenome profiling and editing of neocortical progenitor cells during development
Albert, M., Kalebic, N., Florio, M., Lakshmanaperumal, N., Haffner, C., Brandl, H., Henry, I., & Huttner, W. Β. (2017) · The EMBO Journal · doi:10.15252/embj.201796764 · Cited by 113 · see citing works
Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins
Amin, E., Jaiswal, M., Derewenda, U., Reis, K., Nouri, K., Koessmeier, K. T., Aspenström, P., Somlyo, A. V., Dvorský, R., & Ahmadian, M. R. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.736967 · Cited by 110 · see citing works
Probing human brain evolution and development in organoids
Giandomenico, S. L., & Lancaster, M. A. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.01.001 · Cited by 107 · see citing works
A catalog of single nucleotide changes distinguishing modern humans from archaic hominins
Kuhlwilm, M., & Boeckx, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-44877-x · Cited by 108 · see citing works
Levchenko, А., Kanapin, A. A., Samsonova, A. A., & Gainetdinov, R. R. (2017) · Genome Biology and Evolution · doi:10.1093/gbe/evx240 · Cited by 104 · see citing works
Neural Progenitor Cell Polarity and Cortical Development
Arai, Y., & Taverna, E. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00384 · Cited by 104 · see citing works
Genes and Mechanisms Involved in the Generation and Amplification of Basal Radial Glial Cells
Penisson, M., Ladewig, J., Belvindrah, R., & Francis, F. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00381 · Cited by 97 · see citing works
A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification
Florio, M., Namba, T., Pääbo, S., Hiller, M., & Huttner, W. Β. (2016) · Science Advances · doi:10.1126/sciadv.1601941 · Cited by 99 · see citing works
Sustained Pax6 Expression Generates Primate-like Basal Radial Glia in Developing Mouse Neocortex
Wong, F. K., Fei, J., Mora‐Bermúdez, F., Taverna, E., Haffner, C., Fu, J., Anastassiadis, K., Stewart, A. F., & Huttner, W. Β. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002217 · Cited by 96 · see citing works
A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex
Vaid, S., Camp, J. G., Hersemann, L., Oegema, C. E., Heninger, A., Winkler, S., Brandl, H., Sarov, M., Treutlein, B., Huttner, W. Β., et al. (2018) · Development · doi:10.1242/dev.169276 · Cited by 96 · see citing works
Human-specific genomic signatures of neocortical expansion
Florio, M., Borrell, V., & Huttner, W. Β. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.11.004 · Cited by 96 · see citing works
Human evolution: the non-coding revolution
Franchini, L. F., & Pollard, K. S. (2017) · BMC Biology · doi:10.1186/s12915-017-0428-9 · Cited by 90 · see citing works
Cortical progenitor biology: key features mediating proliferation versus differentiation
Uzquiano, A., Gladwyn-Ng, I. E., Nguyen, L., Reiner, O., Götz, M., Matsuzaki, F., & Francis, F. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14338 · Cited by 89 · see citing works
Species and cell-type properties of classically defined human and rodent neurons and glia
Xu, X., Stoyanova, E. I., Patriotis, A. L., Xing, J., Mash, D. C., & Heintz, N. (2018) · eLife · doi:10.7554/elife.37551 · Cited by 90 · see citing works
Metabolic Regulation of Neocortical Expansion in Development and Evolution
Namba, T., Nardelli, J., Gressèns, P., & Huttner, W. Β. (2020) · Neuron · doi:10.1016/j.neuron.2020.11.014 · Cited by 92 · see citing works
An Incomplete Understanding of Human Genetic Variation
Huddleston, J., & Eichler, E. E. (2016) · Genetics · doi:10.1534/genetics.115.180539 · Cited by 91 · see citing works
Shaping the brain: The emergence of cortical structure and folding
Akula, S. K., Exposito-Alonso, D., & Walsh, C. A. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.11.004 · Cited by 97 · see citing works
Lawson, C. D., Fan, C., Mitin, N., Baker, N. M., George, S. D., Graham, D. M., Perou, C. M., Burridge, K., Der, C. J., & Rossman, K. L. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2923 · Cited by 86 · see citing works
Kalebic, N., Taverna, E., Tavano, S., Wong, F. K., Suchold, D., Winkler, S., Huttner, W. Β., & Sarov, M. (2016) · EMBO Reports · doi:10.15252/embr.201541715 · Cited by 82 · see citing works
Basal Progenitor Morphology and Neocortex Evolution
Kalebic, N., & Huttner, W. Β. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.07.009 · Cited by 85 · see citing works
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review