A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice
Open accessAbstract
It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting that the humanized Foxp2 allele affects basal ganglia. In the striatum, a part of the basal ganglia affected in humans with a speech deficit due to a nonfunctional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one nonfunctional Foxp2 allele show opposite effects, this suggests that alterations in cortico-basal ganglia circuits might have been important for the evolution of speech and language in humans.
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The cortico-striatal circuitry mediates speech and language in humans.
“These findings suggest that the cortico-striatal circuitry mediates speech and language in humans (Enard et al., 2009; Fujita et al., 2008; Schreiweis et al., 2014; Shu et al., 2005).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Enard et al., 2009
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Willi, R., Weinmann, O., Winter, C., Klein, J., Sohr, R., Schnell, L., Yee, B. K., Feldon, J., & Schwab, M. E. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4393-09.2010 · Cited by 52 · see citing works
Self-citationReproducible Computational Workflows with Continuous Analysis
Beaulieu-Jones, B. K., & Greene, C. S. (2016) · doi:10.1101/056473 · Cited by 154 · see citing works
- Authors
- Enard, W., Gehre, S., Hammerschmidt, K., Hölter, S. M., Blass, T., Somel, M., Brückner, M. K., Schreiweis, C., Winter, C., Sohr, R., Becker, L., Wiebe, V., Nickel, B., Giger, T., Müller, U., Groszer, M., Adler, T., Aguilar, A., Bolle, I., Calzada-Wack, J., Dalke, C., Ehrhardt, N., Favor, J., Fuchs, H., Gailus-Durner, V., Hans, W., Hölzlwimmer, G., Javaheri, A., Kalaydjiev, S., Kallnik, M., Kling, E., Kunder, S., Moßbrugger, I., Naton, B., Racz, I., Rathkolb, B., Rozman, J., Schrewe, A., Busch, D. H., Graw, J., Ivandic, B., Klingenspor, M., Klopstock, T., Ollert, M., Quintanilla-Martinez, L., Schulz, H., Wolf, E., Wurst, W., Zimmer, A., Fisher, S. E., Morgenstern, R., Arendt, T., Hrabé de Angelis, M., Fischer, J., Schwarz, J., & Pääbo, S.
- Affiliations
- Max Planck Institute for Evolutionary Anthropology (DE)
- German Primate Center (DE)
- Helmholtz Munich (DE)
- Leipzig University (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Centre for Human Genetics (GB)
- Technical University of Munich (DE)
- Philipps University of Marburg (DE)
- Heidelberg University (DE)
- Ludwig-Maximilians-Universität München (DE)
- University of Bonn (DE)
- California Institute of Technology (US)
- Corresponding author
- Enard, Wolfgang
- ORCID
- Enard, Wolfgang
- Hammerschmidt, Kurt
- Hölter, Sabine M.
- Somel, Mehmet
- Schreiweis, Christiane
- Winter, Christine
- Becker, Lore
- Müller, Uwe
- Groszer, Matthias
- Adler, Thure
- Dalke, Claudia
- Fuchs, Helmut
- Hans, Wolfgang
- Hölzlwimmer, Gabriele
- Kunder, Sandra
- Rathkolb, Birgit
- Rozman, Jan
- Busch, Dirk H.
- Graw, Jochen
- Klingenspor, Martin
- Klopstock, Thomas
- Ollert, Markus
- Schulz, Holger
- Wolf, Eckhard
- Wurst, Wolfgang
- Fisher, Simon E.
- Arendt, Thomas
- Fischer, Julia
- Pääbo, Svante
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 137
- Issue
- 5
- Pages
- 961-971
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2113104616
- Cited by
- 605
- References
- 67
- Citations by year
- 2026: 17 · 2025: 66 · 2024: 14 · 2023: 43 · 2022: 19 · 2021: 17 · 2020: 17 · 2019: 36 · 2018: 34 · 2017: 30 · 2016: 32 · 2015: 56 · 2014: 39 · 2013: 48 · 2012: 50
- FWCI
- 26.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1538 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- OpenMETU (Middle East Technical University) (submittedVersion, cc-by-nc-nd)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- GRO (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Animal Vocal Communication and Behavior
- Social Sciences › Cultural Studies › Language and cultural evolution
- Keywords
- FOXP2, cortico-basal ganglia circuits, basal ganglia, striatum, medium spiny neurons, dendritic length, synaptic plasticity, ultrasonic vocalizations, exploratory behavior, dopamine, positive selection
- MeSH terms
- Animals, Basal Ganglia, Dendrites, Dopamine, Biological Evolution, Heterozygote, Humans, Language, Neural Pathways, Neuronal Plasticity, Speech, Vocalization, Animal, Gene Expression, Amino Acid Substitution, Long-Term Synaptic Depression, Mice, 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 ›
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