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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.
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“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
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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
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