Cited by 390Genetics and Neurodevelopmental DisordersLanguage and cultural evolutionLanguage Development and Disorders

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Human-specific transcriptional regulation of CNS development genes by FOXP2

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Konopka, Genevieve, Bomar, Jamee M., Winden, Kellen, Coppola, Giovanni, Jonsson, Zophonias O., Gao, Fuying, Peng, Sophia, Preuss, Todd M., Wohlschlegel, James A., Geschwind, Daniel H.·2009·Nature

DOI 10.1038/nature08549PMC PMC2778075

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Abstract

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.

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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: Winden, Kellen
Coppola, Giovanni
Gao, Fuying
Peng, Sophia
Preuss, Todd M.
Wohlschlegel, James A.
Geschwind, Daniel H.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-11
Volume: 462
Issue: 7270
Pages: 213-217
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08549
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

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