The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Human-specific transcriptional regulation of CNS development genes by FOXP2
Open accessAbstract
The signalling pathways controlling both the evolution and development of language in the human brain remain unknown. So far, the transcription factor FOXP2 (forkhead box P2) is the only gene implicated in Mendelian forms of human speech and language dysfunction. It has been proposed that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this two-amino-acid change occurred around the time of language emergence in humans. However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here we demonstrate that these two human-specific amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (CNS). Because FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“These amino acid changes are functionally critical as the human and chimpanzee FOXP2 have strikingly different transcriptional targets, many of which are involved in central nervous system development (Konopka et al., 2009).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Konopka et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A General Framework for Weighted Gene Co-Expression Network Analysis
Zhang, B., & Horvath, S. (2005) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1128 · Cited by 5,684
Elias, J. E., & Gygi, S. P. (2007) · Nature Methods · doi:10.1038/nmeth1019 · Cited by 3,925
King, M.-C., & Wilson, A. C. (1975) · Science · doi:10.1126/science.1090005 · Cited by 2,815
A forkhead-domain gene is mutated in a severe speech and language disorder
Lai, C. S. L., Fisher, S. E., Hurst, J. A., Vargha‐Khadem, F., & Monaco, A. P. (2001) · Nature · doi:10.1038/35097076 · Cited by 2,053
A molecular timescale for vertebrate evolution
Kumar, S., & Hedges, S. B. (1998) · Nature · doi:10.1038/31927 · Cited by 1,936
Molecular evolution of FOXP2, a gene involved in speech and language
Enard, W., Przeworski, M., Fisher, S. E., Lai, C. S. L., Wiebe, V., Kitano, T., Monaco, A. P., & Pääbo, S. (2002) · Nature · doi:10.1038/nature01025 · Cited by 1,603
Intra- and Interspecific Variation in Primate Gene Expression Patterns
Enard, W., Khaitovich, P., Klose, J., Zöllner, S. K., Heißig, F., Giavalisco, P., Nieselt, K., Muchmore, E. A., Varki, A. P., Ravid, R., et al. (2002) · Science · doi:10.1126/science.1068996 · Cited by 845
Functional organization of the transcriptome in human brain
Oldham, M. C., Konopka, G., Iwamoto, K., Langfelder, P., Kato, T., Horvath, S., & Geschwind, D. H. (2008) · Nature Neuroscience · doi:10.1038/nn.2207 · Cited by 752
A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice
Enard, W., Gehre, S., Hammerschmidt, K., Hölter, S. M., Blass, T., Somel, M., Brückner, M. K., Schreiweis, C., Winter, C., Sohr, R., et al. (2009) · Cell · doi:10.1016/j.cell.2009.03.041 · Cited by 605
Johnson, M. B., Kawasawa, Y. I., Mason, C. E., Krsnik, Ž., Coppola, G., Bogdanović, D., Geschwind, D. H., Mane, S. M., State, M. W., & Šestan, N. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.027 · Cited by 603
Cited by
Sorted by citations
Items 301–390 of 390
Dediu, D. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781139342872.033 · Cited by 3
A Co-evolved Continuum of Language, Culture and Cognition: Prospects of In-terdisciplinary Research
Nölle, J. (2014) · Studies About Languages · doi:10.5755/j01.sal.0.25.8504 · Cited by 2
Pearson, O. M. (2012) · Cambridge University Press eBooks · doi:10.1017/cbo9781139096164.025 · Cited by 2
Spinelli, E. G., Tempini, M. L. G., & Shapiro, K. A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800105-9.00032-9 · Cited by 2
Language Neuromechanics: The Human Biological-Language Evolution
Chung, D.-Y. (2018) · Journal of Behavioral and Brain Science · doi:10.4236/jbbs.2018.88028 · Cited by 3
Bermejo‐Fenoll, A., Panchón-Ruíz, A., & WALKER, M. J. (2022) · Archaeological and Anthropological Sciences · doi:10.1007/s12520-022-01575-6 · Cited by 2
Wein, W. (2023) · MedienPädagogik Zeitschrift für Theorie und Praxis der Medienbildung · doi:10.21240/mpaed/55/2023.10.06.x · Cited by 2
Cobbe, N., & Wilson, V. A. (2010) · Stem cell biology and regenerative medicine · doi:10.1007/978-1-60761-959-8_15 · Cited by 2
The Molecular Convergence of Birdsong and Speech
Deshpande, M., & Lints, T. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8400-4_6 · Cited by 2
Tendencias actuales de la investigación genómica. Sus perspectivas en Nicaragua
Huete‐Pérez, J. A. (2009) · Encuentro · doi:10.5377/encuentro.v41i84.52 · Cited by 2
Devanna, P., Dediu, D., & Vernes, S. C. (2018) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780198786825.013.37 · Cited by 3
Buried Treasure? Overlooked and Newly Discovered Evolutionary Contributions to Human Brain Diseases
Diederich, N. J., Brüne, M., Allen, J. S., Bender, N., Bruner, E., Changeux, J., Calì, C., Dolgova, O., Grünewald, A., Konopka, G., et al. (2025) · Annals of Neurology · doi:10.1002/ana.78030 · Cited by 1
Li, T., Mo, F., Qi, J., Li, C., Li, X., Zhang, J., Lu, Y., Yao, C., Zhang, L., Hu, B., et al. (2025) · Genomics Proteomics & Bioinformatics · doi:10.1093/gpbjnl/qzaf125 · Cited by 1
Trastornos del lenguaje como oscilopatías
Benítez‐Burraco, A., & Boeckx, C. A. (2014) · Revista de Neurología · doi:10.33588/rn.5907.2014317 · Cited by 1
Homo sapiens under Neutral Evolution
Saitou, N. (2014) · Genes and Environment · doi:10.3123/jemsge.2014.010 · Cited by 1
The Fetal Brain Provides a Raison d’être for the Evolution of New Human Genes
Konopka, G. (2012) · Brain Behavior and Evolution · doi:10.1159/000336723 · Cited by 2
Benítez‐Burraco, A. (2012) · Trabajos de Prehistoria · doi:10.3989/tp.2012.12089 · Cited by 2
The sound of one hand clapping: Overdetermination and the pansensory nature of communication
Aitken, K. J. (2014) · Behavioral and Brain Sciences · doi:10.1017/s0140525x13003944 · Cited by 1
White, S. A. (2013) · Studies in language companion series · doi:10.1075/slcs.144.09whi · Cited by 1
Neuroscience and the Genomic Revolution: An Overview
Parikshak, N., & Geschwind, D. H. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-382227-7.00084-7 · Cited by 1
Components of the Language-Ready Brain
Boeckx, C. A., & Benítez‐Burraco, A. (2016) · Frontiers research topics · doi:10.3389/978-2-88919-893-1 · Cited by 1
Interspecies Mixtures and the Status of Humanity
Cobbe, N. (2011) · Springer eBooks · doi:10.1007/978-3-642-20772-3_9 · Cited by 1
BIOLINGUISTICS: CURRENT STATE AND FUTURE PROSPECTS
Jenkins, L. (2013) · ENGLISH LINGUISTICS · doi:10.9793/elsj.30.2_485 · Cited by 1
Myths of the Baltic Sea eutrophication
Savchuk, O. (2018) · Journal of Aquaculture & Marine Biology · doi:10.15406/jamb.2018.07.00190 · Cited by 1
Crocco, P., Rango, F. D., Bruno, F., Malvaso, A., Maletta, R., Bruni, A. C., Passarino, G., Rose, G., & Dato, S. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e31624 · Cited by 2
Relationship between Cognition, levels of PTX-3, MBL and their polymorphisms: A systematic review
Carvalho, T. L., Belmont, T. F. D. M., da Silva, A. S., do Ó, K. P., Silva, L. D. L. S. E., de Lima, E. A., Vasconcelos, L. R. S., de Moura, P. M. M. F., & Correia, C. D. C. (2020) · Research Society and Development · doi:10.33448/rsd-v9i10.9215
Rebelo, M. Â., Gómez, C., Gomes, I., Poza, J., Martins, S., Maturana-Candelas, A., Ruiz-Gómez, S. J., Durães, L., Sousa, P., Figueruelo, M., et al. (2020) · Brain Sciences · doi:10.3390/brainsci10110870 · Cited by 1
Graw, J. (2020) · Springer eBooks · doi:10.1007/978-3-662-60909-5_15 · Cited by 1
FOXP2 and the Genetic and Developmental Basis of Human Language
Lalueza‐Fox, C. (2015) · doi:10.1002/9781118524756.ch12 · Cited by 1
The Role of Vocal Learning in Language. Evolution and Development
Zhang, Q. (2017) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · Cited by 1
On the Interaction of Information and Matter: The Case Study about the Language and BrainPreprint
Chen, L., Liu, Y., Chen, J., Li, X., & Di, Z. (2018) · Preprints.org · doi:10.20944/preprints201812.0365.v1
Let Sing Again. Of Sounds, Songs, and Language in Humans and BirdsPreprint
di Porzio, U., & Speranza, L. (2020) · Preprints.org · doi:10.20944/preprints202010.0065.v1 · Cited by 1
(2011) · Wiley eBooks · doi:10.1002/9781444342499.refs · Cited by 1
The Convergence of Intelligence and LongevityPreprint
Gualtieri, C. (2024) · Qeios · doi:10.32388/wvwb0l
Eick, L., FinnGen, Ganna, A., & Yang, Z. (2025) · medRxiv · doi:10.64898/2025.12.14.25342213 · Cited by 1
Murugan, M. (2013) · DukeSpace (Duke University)
Graw, J. (2015) · Springer eBooks · doi:10.1007/978-3-662-44817-5_15
Tremberger, G., Dehipawala, S., Cheung, E., Holden, T. M., Sullivan, R., Nguyen, N. A., Lieberman, D., & Cheung, T. (2015) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.2186563
Caminhando com os fundamentos da gramática gerativa
França, A. I., & Lage, A. C. (2015) · Confluência · doi:10.18364/rc.v1i47.33
Whalley, K. (2009) · Nature reviews. Neuroscience · doi:10.1038/nrn2775
Differences in Speech Gene Deciphered in Humans and Chimps
Talan, J. (2009) · Neurology Today · doi:10.1097/01.nt.0000366066.52720.7c
Evidence for gliadin antibodies as causative agents in schizophrenia.Preprint
Carter, C., & Carter, C. (2010) · Nature Precedings · doi:10.1038/npre.2010.5351.1
Revealing miRNA Regulation and miRNA Target Prediction Using Constraint-Based Learning
Alshalalfa, M., Tan, M., Naji, G., Alhajj, R., Polat, F., & Rokne, J. G. (2012) · IEEE Transactions on Systems Man and Cybernetics Part C (Applications and Reviews) · doi:10.1109/tsmcc.2012.2186801
Biología y Lenguaje: pasado, presente y futuro de una relación obligada
Benítez‐Burraco, A. (2011) · University of Valladolid Documentary Repository (University of Valladolid)
Graduate Program in Bioinformatics and Genome Technology
Wang, R. (2011)
Uriagereka, J. (2011) · doi:10.1093/acprof:oso/9780199593521.003.0008
Uriagereka, J. (2011) · doi:10.1093/acprof:oso/9780199593521.003.0007
Uriagereka, J. (2011) · doi:10.1093/acprof:oso/9780199593521.003.0006
COGNITIVE DOMAINS FUNCTION COMPLEMENTATION
Paralogs, N. G., Prosselkov, P., Polygalov, D., Zhang, Q., & McHugh, T. J. (2015)
Naslavsky, M. S. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.41.2016.tde-14012016-092908
Benítez‐Burraco, A., & Martínez, V. M. L. (2011)
Molecular Mechanisms Regulating Mammalian Forebrain Development
Tsui, D. C. C. (2014) · TSpace (University of Toronto)
What Lenneberg Got Right: A Homological Program for the Study of Language Evolution
Balari, S., & Lorenzo, G. (2017) · Biolinguistics · doi:10.5964/bioling.9083
The role of FoxP2 in striatal circuitry
van Rhijn, J.-R. (2019) · MPG.PuRe (Max Planck Society)
Genetic Footprints of Natural Selection and Drift in Human Evolution
Somel, M., & Sezgın, E. (2010) · DergiPark (Istanbul University)
An overview on the evolution of language and genetics of speech disorders
Mousavi, S. M., Kamali, E., Karimi, P., & Salehi, M. (2014)
Anderson, S. R. (2020) · Historiographia Linguistica · doi:10.1075/hl.00051.and
FITCH, R. H. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-397267-5.00116-3
Análisis comparativo entre la capacidad innata y la adquisición de la primera lengua
Villamil, N. S., & Rodríguez, J. R. (2011)
Delving into the genetic causes of language impairment in people with partial deletions of NRXN1Preprint
Benítez‐Burraco, A., Jiménez-Romero, M. S., & Fernández-Urquiza, M. (2022) · doi:10.31234/osf.io/aw25n
Saitou, N. (2018) · Computational biology · doi:10.1007/978-3-319-92642-1_6
Клягин Н.В. П. Рикёр и историческая истина
Н.В., К. (2013) · Философия и культура · doi:10.7256/1999-2793.2013.11.9130
Uriagereka, J. (2011) · doi:10.1093/acprof:oso/9780199593521.003.0005
Hillert, D. G. (2017) · Springer eBooks · doi:10.1007/978-3-658-20113-5_4
FITCH, R. H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-814409-1.00014-8
Uriagereka, J. (2011) · doi:10.1093/acprof:oso/9780199593521.003.0004
Boeckx, C. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-820584-6.00038-6
Uriagereka, J. (2011) · doi:10.1093/acprof:oso/9780199593521.003.0003
Uriagereka, J. (2011) · doi:10.1093/acprof:oso/9780199593521.003.0001
Hillert, D. G. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0609-3_3
Uriagereka, J. (2011) · doi:10.1093/acprof:oso/9780199593521.003.0002
Jones, M. (2022) · Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) · doi:10.21248/gups.71574
Shimada, M., Omae, Y., Kakita, A., Gabdulkhaev, R., Miyagawa, T., Honda, M., Fujimoto, A., & Tokunaga, K. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.13.540603
Konopka, G., & Caglayan, E. (2024) · Oxford University Press eBooks · doi:10.1093/med/9780197676592.003.0006
Comprehensive Characterization of the Promoter Proximal Proteome of Single Copy Locus FOXP2Preprint
MacKenzie, T. M. G., Ramirez, L., Jian, R., Jiang, L., & Snyder, M. P. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.10.663086
Gene expression changes in human brain evolution
Berto, S., Yi, S. V., & Konopka, G. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-27380-3.00057-9
Evolution of Mammalian Regulatory Networks in the Brain
Ganesan, R., & Pfenning, A. R. (2025) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-111523-102317
Mouillet‐Richard, S., Gougèlet, A., Passet, B., Brochard, C., Corre, D. L., Pitasi, C. L., Joubel, C., Sroussi, M., Gallois, C., Lavergne, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25566247
Ehrenhofer‐Murray, A. E. (2025) · Springer eBooks · doi:10.1007/978-3-662-70328-1_15
Wu, Z., Yuan, Z., Yang, R., Huang, Z., Liu, Y., Sun, L., Bian, Z., & He, M. (2026) · medRxiv · doi:10.64898/2026.04.07.26350283
A LINE-1 insertion upstream of FOXP2 promotes neuronal differentiation during primate evolution
Liu, J., Yin, Z., Peng, Y., Cui, S., Shi, B., Jiang, X., Yang, Z., Gu, S., Lin, Y., Xu, L., et al. (2026) · Genome biology · doi:10.1186/s13059-026-04098-8
What makes human cortex human? Rephrasing the question to consider numbers of neurons
Herculano-Houzel, S. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27380-3.00079-8
Ponomareva, O. Y., Seabrook, L. T., Maya-Martínez, M., Klengel, C., Balakundi, V., Kini, S., Catt, E., Zion, J., Shah, R., Gonzalez, P. M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.22.733764
Song, F., Li, X., Cheng, C., & Du, J. (2026) · Journal of Neural Transmission · doi:10.1007/s00702-026-03160-w
Jankovic, M. J., Huang, Y.-T., Holley, A. J., Kirkland, S., Kulkarni, A., Sakano, H., Gibson, J. R., & Konopka, G. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.18.739349
Regulatory Evolution and the Genetic Basis of Human Brain Expansion
Hettiarachchi, N. (2026) · Journal of Molecular Evolution · doi:10.1007/s00239-026-10344-1
Ulmschneider, P. (2013) · Springer eBooks · doi:10.1007/978-3-642-29926-1_9
Metadata
- Authors
- Konopka, G., Bomar, J. M., Winden, K., Coppola, G., Jonsson, Z. O., Gao, F., Peng, S., Preuss, T. M., Wohlschlegel, J. A., & Geschwind, D. H.
- Affiliations
- Emory University (US)
- University of California, Los Angeles (US)
- Corresponding author
- Geschwind, Daniel H.
- ORCID
- Venue
- Nature
- Published
- 2009-11
- Volume
- 462
- Issue
- 7270
- Pages
- 213-217
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2778075
- OpenAlex
- W2012332159
- Cited by
- 390
- References
- 31
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 12 · 2023: 11 · 2022: 10 · 2021: 8 · 2020: 18 · 2019: 12 · 2018: 28 · 2017: 21 · 2016: 27 · 2015: 30 · 2014: 35 · 2013: 31 · 2012: 50
- FWCI
- 24.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R37MH60233-06A1, R21MH075028, T32MH073526, R37MH060233)
- National Center for Research Resources (RR-00 165, P51RR000165)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (N01 HD 43383, N01-HD-4-3368, T32HD007032)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Cultural Studies › Language and cultural evolution
- Social Sciences › Psychology › Developmental and Educational Psychology › Language Development and Disorders
- Keywords
- FOXP2, transcriptional regulation, chimpanzees, human brain development, language evolution, transcription factor target genes, gene regulatory networks, central nervous system disorders, speech and language disorders, human-chimpanzee comparison
- MeSH terms
- Animals, Brain, Cell Line, Pan troglodytes, Humans, Language, Promoter Regions, Genetic, Species Specificity, Speech, Transcription, Genetic, Transcriptional Activation, Gene Expression Regulation, Developmental, Evolution, Molecular, Forkhead Transcription Factors
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
