Human-specific transcriptional regulation of CNS development genes by FOXP2

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.

doi:10.1038/nature08549

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

Human-specific transcriptional regulation of CNS development genes by FOXP2

Open access

Konopka, Genevieve, Bomar, Jamee M., Winden, Kellen, Coppola, Giovanni, Jonsson, Zophonias O., Gao, Fuying, Peng, Sophia, Preuss, Todd M. +2 more·2009·Nature

DOI 10.1038/nature08549PMC PMC2778075

Open this paper in CoChat — free account

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.

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

Crossref · 10.1038/nature08549

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

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?

Human and chimpanzee FOXP2 have strikingly different transcriptional targets, many of which are involved in central nervous system development.
“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.

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 · see citing works
Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry
Elias, J. E., & Gygi, S. P. (2007) · Nature Methods · doi:10.1038/nmeth1019 · Cited by 3,925 · see citing works
Evolution at Two Levels in Humans and Chimpanzees: Their macromolecules are so alike that regulatory mutations may account for their biological differences
King, M.-C., & Wilson, A. C. (1975) · Science · doi:10.1126/science.1090005 · Cited by 2,815 · see citing works
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 · see citing works
A molecular timescale for vertebrate evolution
Kumar, S., & Hedges, S. B. (1998) · Nature · doi:10.1038/31927 · Cited by 1,936 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Functional and Evolutionary Insights into Human Brain Development through Global Transcriptome Analysis
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 · see citing works
Elevated gene expression levels distinguish human from non-human primate brains
Cáceres, M., Lachuer, J., Zapala, M. A., Redmond, J. C., Kudo, L., Geschwind, D. H., Lockhart, D. J., Preuss, T. M., & Barlow, C. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2135499100 · Cited by 491 · see citing works
Expansion of a novel CAG trinucleotide repeat in the 5′ region of PPP2R2B is associated with SCA12
Holmes, S. E., O’Hearn, E., McInnis, M. G., Gorelick-Feldman, D. A., Kleiderlein, J. J., Callahan, C., Kwak, N. G., Ingersoll, R., Sherr, M., Sumner, A. J., et al. (1999) · Nature Genetics · doi:10.1038/70493 · Cited by 488 · see citing works
Accelerated Evolution of Conserved Noncoding Sequences in Humans
Prabhakar, S., Noonan, J. P., Pääbo, S., & Rubin, E. M. (2006) · Science · doi:10.1126/science.1130738 · Cited by 481 · see citing works
Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5
Acampora, D., Merlo, G. R., Paleari, L., Zerega, B., Postiglione, M. P., Mantero, S., Bober, E., Barbieri, O., Simeone, A., & Levi, G. (1999) · Development · doi:10.1242/dev.126.17.3795 · Cited by 444 · see citing works
Accelerated Evolution of Nervous System Genes in the Origin of Homo sapiens
Dorus, S., Vallender, E. J., Evans, P. D., Anderson, J. R., Gilbert, S. L., Mahowald, M. A., Wyckoff, G. J., Malcom, C. M., & Lahn, B. T. (2004) · Cell · doi:10.1016/j.cell.2004.11.040 · Cited by 428 · see citing works
Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene
Shu, W., Cho, J. Y., Jiang, Y., Zhang, M., Weisz, D. J., Elder, G. A., Schmeidler, J., Gasperi, R. D., Sosa, M. A. G., Rabidou, D., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503739102 · Cited by 415 · see citing works
Identification of FOXP2 Truncation as a Novel Cause of Developmental Speech and Language Deficits
MacDermot, K. D., Bonora, E., Sykes, N., Coupe, A., Lai, C. S. L., Vernes, S. C., Vargha‐Khadem, F., McKenzie, F., Smith, R. L., Monaco, A. P., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/430841 · Cited by 411 · see citing works
Transcriptional and DNA Binding Activity of the Foxp1/2/4 Family Is Modulated by Heterotypic and Homotypic Protein Interactions
Li, S., Weidenfeld, J., & Morrisey, E. E. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.24.2.809-822.2004 · Cited by 333 · see citing works
Identification of the Transcriptional Targets of FOXP2, a Gene Linked to Speech and Language, in Developing Human Brain
Spiteri, E., Konopka, G., Coppola, G., Bomar, J. M., Oldham, M. C., Ou, J., Vernes, S. C., Fisher, S. E., Ren, B., & Geschwind, D. H. (2007) · The American Journal of Human Genetics · doi:10.1086/522237 · Cited by 281 · see citing works
Mutations in the Gene Encoding Gap Junction Protein α12 (Connexin 46.6) Cause Pelizaeus-Merzbacher–Like Disease
Uhlenberg, B., Schuelke, M., Rüschendorf, F., Ruf, N., Kaindl, A. M., Henneke, M., Thiele, H., Stoltenburg, G., Aksu, F., Topaloğlu, H., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/422763 · Cited by 271 · see citing works
High-Throughput Analysis of Promoter Occupancy Reveals Direct Neural Targets of FOXP2, a Gene Mutated in Speech and Language Disorders
Vernes, S. C., Spiteri, E., Nicod, J., Groszer, M., Taylor, J. M., Davies, K. E., Geschwind, D. H., & Fisher, S. E. (2007) · The American Journal of Human Genetics · doi:10.1086/522238 · Cited by 268 · see citing works
Accelerated Protein Evolution and Origins of Human-Specific Features: FOXP2 as an Example
Zhang, J., Webb, D., & Podlaha, O. (2002) · Genetics · doi:10.1093/genetics/162.4.1825 · Cited by 252 · see citing works
Absence of a Paternally Inherited FOXP2 Gene in Developmental Verbal Dyspraxia
Feuk, L., Kalervo, A., Lipsanen‐Nyman, M., Skaug, J., Nakabayashi, K., Finucane, B. M., Hartung, D., Innes, A. M., Kerem, B., Nowaczyk, M. J. M., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/508902 · Cited by 186 · see citing works
A New Autosomal Recessive Form of Stickler Syndrome Is Caused by a Mutation in the COL9A1 Gene
Camp, G. V., Snoeckx, R. L., Hilgert, N., van den Ende, J., Fukuoka, H., Wagatsuma, M., Suzuki, H., Smets, R. M. E., Vanhoenacker, F. M. H. M., Declau, F., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/506478 · Cited by 182 · see citing works
Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia
Pagnamenta, E., Salmond, C. H., Watkins, K. E., Vargha‐Khadem, F., & Gadian, D. G. (2003) · Human Brain Mapping · doi:10.1002/hbm.10093 · Cited by 162 · see citing works
Retrograde Signaling by Syt 4 Induces Presynaptic Release and Synapse-Specific Growth
Yoshihara, M., Adolfsen, B., Galle, K. T., & Littleton, J. T. (2005) · Science · doi:10.1126/science.1117541 · Cited by 153 · see citing works
Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): A new phenotype
Brusse, E., de Koning, I., Maat-Kievit, A., Oostra, B., Heutink, P., & van Swieten, J. V. (2006) · Movement Disorders · doi:10.1002/mds.20708 · Cited by 115 · see citing works
Gene expression study on peripheral blood identifies progranulin mutations
Coppola, G., Karydas, A., Rademakers, R., Wang, Q., Baker, M. C., Hutton, M., Miller, B. L., & Geschwind, D. H. (2008) · Annals of Neurology · doi:10.1002/ana.21397 · Cited by 87 · see citing works
Identification of SUMO-Conjugated Proteins and their SUMO Attachment Sites Using Proteomic Mass Spectrometry
Wohlschlegel, J. A. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-566-4_3 · Cited by 77 · see citing works
Junctional Adhesion Molecule-A Is Critical for the Formation of Pseudocanaliculi and Modulates E-cadherin Expression in Hepatic Cells
Konopka, G., Tekiela, J., Iverson, M., Wells, C. W., & Duncan, S. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703592200 · Cited by 51 · see citing works
Expression and network analysis of Illumina microarray data
Coppola, G., Winden, K. D., Konopka, G., Gao, F., & Geschwind, D. H. (2009) · Protocol Exchange · doi:10.1038/nprot.2009.215 · Cited by 1 · see citing works

Flagged first, then by citations

Sorted by citations

Cortical Evolution: Judge the Brain by Its Cover
Geschwind, D. H., & Rakic, P. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.045 · Cited by 519 · see citing works
Altered proliferation and networks in neural cells derived from idiopathic autistic individuals
Marchetto, M. C., Belinson, H., Tian, Y., Freitas, B. C., Fu, C., Vadodaria, K. C., Beltrao-Braga, P. C., Trujillo, C. A., Mendes, A. P. D., Padmanabhan, K., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.95 · Cited by 466 · see citing works
Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation
Charrier, C., Joshi, K., Coutinho-Budd, J., Kim, J.-E., Lambert, N., de Marchena, J., Jin, W.-L., Vanderhaeghen, P., Ghosh, A., Sassa, T., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.034 · Cited by 454 · see citing works
Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways
Miller, J. A., Horvath, S., & Geschwind, D. H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914257107 · Cited by 480 · see citing works
Self-citation
Genomic Variation in Seven Khoe-San Groups Reveals Adaptation and Complex African History
Schlebusch, C. M., Skoglund, P., Sjödin, P., Gattepaille, L. M., Hernandez, D. G., Jay, F., Li, S., de Jongh, M., Singleton, A., Blum, M. G. B., et al. (2012) · Science · doi:10.1126/science.1227721 · Cited by 457 · see citing works
Convergent transcriptional specializations in the brains of humans and song-learning birds
Pfenning, A. R., Hara, E., Whitney, O., Rivas, M. V., Wang, R., Roulhac, P. L., Howard, J. T., Wirthlin, M., Lovell, P. V., Ganapathy, G., et al. (2014) · Science · doi:10.1126/science.1256846 · Cited by 463 · see citing works
Twitter evolution: converging mechanisms in birdsong and human speech
Bolhuis, J., Okanoya, K., & Scharff, C. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2931 · Cited by 440 · 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
Modeling the cultural evolution of language
Steels, L. (2011) · Physics of Life Reviews · doi:10.1016/j.plrev.2011.10.014 · Cited by 305 · see citing works
Foxp2 regulates gene networks implicated in neurite outgrowth in the developing brain
Vernes, S. C., Oliver, P. L., Spiteri, E., Lockstone, H. E., Puliyadi, R., Taylor, J. M., Ho, J., Mombereau, C., Brewer, A., Lowy, E., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002145 · Cited by 276 · see citing works
Human-Specific Transcriptional Networks in the Brain
Konopka, G., Friedrich, T., Davis‐Turak, J., Winden, K. D., Oldham, M. C., Gao, F., Chen, L., Wang, G.-Z., Luo, R., Preuss, T. M., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.05.034 · Cited by 264 · see citing works
De Novo Mutations in FOXP1 in Cases with Intellectual Disability, Autism, and Language Impairment
Hamdan, F. F., Daoud, H., Rochefort, D., Piton, A., Gauthier, J., Langlois, M., Foomani, G., Dobrzeniecka, S., Krebs, M.-O., Joober, R., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.09.017 · Cited by 235 · see citing works
Human brain evolution: transcripts, metabolites and their regulators
Somel, M., Liu, X., & Khaitovich, P. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3372 · Cited by 243 · see citing works
RBFOX1 regulates both splicing and transcriptional networks in human neuronal development
Fogel, B. L., Wexler, E., Wahnich, A., Friedrich, T., Vijayendran, C., Gao, F., Parikshak, N., Konopka, G., & Geschwind, D. H. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds240 · Cited by 216 · see citing works
Self-citation
Ultrasonic vocalizations in mouse models for speech and socio-cognitive disorders: insights into the evolution of vocal communication
Fischer, J., & Hammerschmidt, K. (2010) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2010.00610.x · Cited by 204 · see citing works
MSC-Regulated MicroRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer Metastasis
Cuiffo, B., Campagne, A., Bell, G. W., Lembo, A., Orso, F., Lien, E. C., Bhasin, M., Raimo, M., Hanson, S. E., Marusyk, A., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.10.001 · Cited by 173 · see citing works
Overlaps Between Autism and Language Impairment: Phenomimicry or Shared Etiology?
Bishop, D. V. M. (2010) · Behavior Genetics · doi:10.1007/s10519-010-9381-x · Cited by 169 · see citing works
Genomic Perspectives of Transcriptional Regulation in Forebrain Development
Nord, A. S., Pattabiraman, K., Visel, A., & Rubenstein, J. L. R. (2015) · Neuron · doi:10.1016/j.neuron.2014.11.011 · Cited by 152 · see citing works
Genetic Variants ofFOXP2andKIAA0319/TTRAP/THEM2Locus Are Associated with Altered Brain Activation in Distinct Language-Related Regions
Pinel, P., Fauchereau, F., Moreno, A., Barbot, A., Lathrop, M. G., Zélénika, D., Bihan, D. L., Poline, J., Bourgeron, T., & Dehaene, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5996-10.2012 · Cited by 160 · see citing works
No Evidence for Recent Selection at FOXP2 among Diverse Human Populations
Atkinson, E. G., Audesse, A. J., Palacios, J. A., Bobo, D., Webb, A. E., Ramachandran, S., & Henn, B. M. (2018) · Cell · doi:10.1016/j.cell.2018.06.048 · Cited by 155 · see citing works
FoxP2 Regulates Neurogenesis during Embryonic Cortical Development
Tsui, D. C. C., Vessey, J. P., Tomita, H., Kaplan, D. R., & Miller, F. D. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1665-12.2013 · Cited by 151 · see citing works
FOXP2 and the role of cortico-basal ganglia circuits in speech and language evolution
Enard, W. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.04.008 · Cited by 149 · see citing works
Autism-Associated Promoter Variant in MET Impacts Functional and Structural Brain Networks
Rudie, J. D., Hernandez, L. M., Brown, J. A., Beck-Pancer, D., Colich, N. L., Gorrindo, P., Thompson, P. M., Geschwind, D. H., Bookheimer, S. Y., Levitt, P., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.010 · Cited by 142 · see citing works
How Language Began: Gesture and Speech in Human Evolution
McNeill, D. (2012) · Cited by 147 · see citing works
Genetic Changes Shaping the Human Brain
Bae, B.-I., Jayaraman, D., & Walsh, C. A. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.01.035 · Cited by 135 · see citing works
A Gene Co-Expression Network in Whole Blood of Schizophrenia Patients Is Independent of Antipsychotic-Use and Enriched for Brain-Expressed Genes
de Jong, S., Boks, M. P., Fuller, T. F., Strengman, E., Janson, E., de Kovel, C. G. F., Ori, A. P. S., Vi, N., Mulder, F., Blom, J. D., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039498 · Cited by 143 · see citing works
The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders
Bacon, C., & Rappold, G. (2012) · Human Genetics · doi:10.1007/s00439-012-1193-z · Cited by 142 · see citing works
The human brain: rewired and running hot
Preuss, T. M. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06001.x · Cited by 132 · see citing works
Renewed focus on the developing human neocortex
Clowry, G. J., Molnár, Z., & RAKIC, P. T. (2010) · Journal of Anatomy · doi:10.1111/j.1469-7580.2010.01281.x · Cited by 141 · see citing works
The Songbird as a Model for the Generation and Learning of Complex Sequential Behaviors
Fee, M. S., & Scharff, C. (2010) · ILAR Journal · doi:10.1093/ilar.51.4.362 · Cited by 138 · see citing works
Foxp2 Mediates Sex Differences in Ultrasonic Vocalization by Rat Pups and Directs Order of Maternal Retrieval
Bowers, J. M., Perez‐Pouchoulen, M., Edwards, N. S., & McCarthy, M. M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0425-12.2013 · Cited by 135 · see citing works
Decoding the genetics of speech and language
Graham, S. A., & Fisher, S. E. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.11.006 · Cited by 130 · see citing works
Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph
Hubisz, M. J., Williams, A. L., & Siepel, A. (2020) · PLOS Genetics · doi:10.1371/journal.pgen.1008895 · Cited by 130 · see citing works
Cerebral cortical development in rodents and primates
Molnár, Z., & Clowry, G. J. (2012) · Progress in brain research · doi:10.1016/b978-0-444-53860-4.00003-9 · Cited by 130 · see citing works
Functional Genomic Analyses Identify Pathways Dysregulated by Progranulin Deficiency, Implicating Wnt Signaling
Rosen, E. Y., Wexler, E. M., Versano, R., Coppola, G., Gao, F., Winden, K. D., Oldham, M. C., Martens, L. H., Zhou, P., Farese, R. V., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.021 · Cited by 128 · see citing works
Diminished FoxP2 Levels Affect Dopaminergic Modulation of Corticostriatal Signaling Important to Song Variability
Murugan, M., Harward, S. C., Scharff, C., & MOONEY, R. D. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.021 · Cited by 124 · see citing works
Human-Specific Histone Methylation Signatures at Transcription Start Sites in Prefrontal Neurons
Shulha, H. P., Crisci, J. L., Reshetov, D. A., Tushir, J. S., Cheung, I. K., Bharadwaj, R. A., Chou, H.-J., Houston, I. B., Peter, C. J., Mitchell, A., et al. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001427 · Cited by 123 · see citing works
FoxP1 orchestration of ASD-relevant signaling pathways in the striatum
Araujo, D. J., Anderson, A. G., Berto, S., Runnels, W., Harper, M., Ammanuel, S., Rieger, M. A., Huang, H.-C., Rajkovich, K., Loerwald, K. W., et al. (2015) · Genes & Development · doi:10.1101/gad.267989.115 · Cited by 111 · see citing works
Evo-devo, deep homology and FoxP2: implications for the evolution of speech and language
Scharff, C., & Petri, J. (2011) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2011.0001 · Cited by 118 · see citing works
Brain diversity evolves via differences in patterning
Sylvester, J. B., Rich, C. A., Loh, Y. E., van Staaden, M. J., Fraser, G. J., & Streelman, J. T. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000395107 · Cited by 118 · see citing works
In vivo human adipose-derived mesenchymal stem cell tracking after intra-articular delivery in a rat osteoarthritis model
Li, M., Luo, X., Lv, X., Liu, V., Zhao, G., Zhang, X., Cao, W., Wang, R., & Wang, W. (2016) · Stem Cell Research & Therapy · doi:10.1186/s13287-016-0420-2 · Cited by 117 · see citing works
Regulation of MET by FOXP2, Genes Implicated in Higher Cognitive Dysfunction and Autism Risk
Mukamel, Z., Konopka, G., Wexler, E., Osborn, G. E., Dong, H., Bergman, M. Y., Levitt, P. R., & Geschwind, D. H. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0181-11.2011 · Cited by 116 · see citing works
Multiple modes of chromatin remodeling by Forkhead box proteins
Lalmansingh, A. S., Karmakar, S., Jin, Y., & Nagaich, A. K. (2012) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2012.02.018 · Cited by 120 · see citing works
Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex
Roll, P., Vernes, S. C., Bruneau, N., Cillario, J., Ponsole-Lenfant, M., Massacrier, A., Rudolf, G., Khalifé, M., Hirsch, É., Fisher, S. E., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq415 · Cited by 114 · see citing works
Spell‐Out and the Minimalist Program
Uriagereka, J. (2011) · doi:10.1093/acprof:oso/9780199593521.001.0001 · Cited by 113 · see citing works
Cultural transmission of vocal dialect in the naked mole-rat
Barker, A. J., Veviurko, G., Bennett, N. C., Hart, D. W., Mograby, L., & Lewin, G. R. (2021) · Science · doi:10.1126/science.abc6588 · Cited by 111 · see citing works
Human brain evolution: From gene discovery to phenotype discovery
Preuss, T. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201894109 · Cited by 108 · see citing works
Molecular Microcircuitry Underlies Functional Specification in a Basal Ganglia Circuit Dedicated to Vocal Learning
Hilliard, A. T., Miller, J. E., Fraley, E., Horvath, S., & White, S. A. (2012) · Neuron · doi:10.1016/j.neuron.2012.01.005 · Cited by 105 · see citing works
Human Accelerated Regions and Other Human-Specific Sequence Variations in the Context of Evolution and Their Relevance for Brain Development
Levchenko, А., Kanapin, A. A., Samsonova, A. A., & Gainetdinov, R. R. (2017) · Genome Biology and Evolution · doi:10.1093/gbe/evx240 · Cited by 103 · see citing works
FoxP influences the speed and accuracy of a perceptual decision in Drosophila
Dasgupta, S., Ferreira, C. H., & Miesenböck, G. (2014) · Science · doi:10.1126/science.1252114 · Cited by 102 · see citing works
Evolution of Transcription Networks — Lessons from Yeasts
Li, H., & Johnson, A. D. (2010) · Current Biology · doi:10.1016/j.cub.2010.06.056 · Cited by 95 · see citing works
Recent advances in the genetics of language impairment
Newbury, D. F., Fisher, S. E., & Monaco, A. P. (2010) · Genome Medicine · doi:10.1186/gm127 · Cited by 98 · see citing works
More than 500,000 years of right-handedness in Europe
Frayer, D. W., Lozano, M., de Castro, J. M. B., Carbonell, E., Arsuaga, J. L., Radovčić, J., Fiore, I., & Bondioli, L. (2011) · Laterality Asymmetries of Body Brain and Cognition · doi:10.1080/1357650x.2010.529451 · Cited by 96 · see citing works
Insights into the Neural and Genetic Basis of Vocal Communication
Konopka, G., & Roberts, T. F. (2016) · Cell · doi:10.1016/j.cell.2016.02.039 · 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
Convergent Pathways in Idiopathic Autism Revealed by Time Course Transcriptomic Analysis of Patient-Derived Neurons
DeRosa, B. A., Hokayem, J. A. E., Artimovich, E., Garcia‐Serje, C., Phillips, A. W., Booven, D. V., Nestor, J. E., Wang, L., Cuccaro, M. L., Vance, J. M., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-26495-1 · Cited by 90 · see citing works
Human brain evolution writ large and small
Sherwood, C. C., Bauernfeind, A. L., Bianchi, S., Raghanti, M. A., & Hof, P. R. (2012) · Progress in Brain Research · doi:10.1016/b978-0-444-53860-4.00011-8 · Cited by 113 · see citing works
The Transcription Factor Ultraspiracle Influences Honey Bee Social Behavior and Behavior-Related Gene Expression
Ament, S. A., Wang, Y., Chen, C.-C., Blatti, C. A., Hong, F., Liang, Z., Nègre, N., White, K. P., Rodriguez‐Zas, S. L., Mizzen, C. A., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002596 · Cited by 87 · see citing works
Genetics of Speech and Language Disorders
Kang, C. P., & Drayna, D. T. (2011) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090810-183119 · Cited by 88 · see citing works
Evolution of transcriptional enhancers and animal diversity
Rubinstein, M., & de Souza, F. S. J. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0017 · Cited by 78 · see citing works
Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity
Galazo, M. J., Emsley, J. G., & Macklis, J. D. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.024 · Cited by 80 · see citing works
Modeling the functional genomics of autism using human neurons
Konopka, G., Wexler, E., Rosen, E., Mukamel, Z., Osborn, G. E., Chen, L., Lu, D., Gao, F., Gao, K., Lowe, J. K., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.60 · Cited by 76 · see citing works
Identifying Key Features of Effective Active Learning: The Effects of Writing and Peer Discussion
Linton, D., Pangle, W. M., Wyatt, K. H., Powell, K. N., & Sherwood, R. E. (2014) · CBE—Life Sciences Education · doi:10.1187/cbe.13-12-0242 · Cited by 82 · see citing works
Right handed Neandertals: Vindija and beyond.
Frayer, D. W., Fiore, I., Lalueza‐Fox, C., Radovčić, J., & Bondioli, L. (2010) · PubMed · Cited by 77 · see citing works
Dendritic Integration of Sensory Evidence in Perceptual Decision-Making
Groschner, L. N., Hak, L. C. W., Bogacz, R., Dasgupta, S., & Miesenböck, G. (2018) · Cell · doi:10.1016/j.cell.2018.03.075 · Cited by 77 · see citing works
A Systems Level, Functional Genomics Analysis of Chronic Epilepsy
Winden, K. D., Karsten, S. L., Bragin, A., Kudo, L. C., Gehman, L., Ruidera, J., Geschwind, D. H., & Engel, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020763 · Cited by 76 · see citing works
Convergent differential regulation of SLIT-ROBO axon guidance genes in the brains of vocal learners
Wang, R., Chen, C., Hara, E., Rivas, M. V., Roulhac, P. L., Howard, J. T., Chakraborty, M., Audet, J., & Jarvis, E. D. (2015) · Journal of Comparative Neurology · doi:10.1002/cne.23719 · Cited by 74 · see citing works
Core and shell song systems unique to the parrot brain
Chakraborty, M., Walløe, S., Nedergaard, S., Fridel, E. E., Dabelsteen, T., Pakkenberg, B., Bertelsen, M. F., Dorrestein, G. M., Brauth, S. E., Durand, S. E., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0118496 · Cited by 86 · see citing works
Genes Expressed in Specific Areas of the Human Fetal Cerebral Cortex Display Distinct Patterns of Evolution
Lambert, N., Lambot, M.-A., Bilheu, A., Albert, V., Englert, Y., Libert, F., Noel, J.-C., Sotiriou, C., Holloway, A. K., Pollard, K. S., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017753 · Cited by 73 · see citing works
Molecular features driving cellular complexity of human brain evolution
Caglayan, E., Ayhan, F., Liu, Y., Vollmer, R. M., Oh, E., Sherwood, C. C., Preuss, T. M., Yi, S. V., & Konopka, G. (2023) · Nature · doi:10.1038/s41586-023-06338-4 · Cited by 67 · see citing works
Transcriptional Regulation by FOXP1, FOXP2, and FOXP4 Dimerization
Sin, C., Li, H., & Crawford, D. A. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0359-7 · Cited by 73 · see citing works
Vocal tract anatomy and the neural bases of talking
LIEBERMAN, P. H. (2012) · Journal of Phonetics · doi:10.1016/j.wocn.2012.04.001 · Cited by 68 · see citing works
Globularity and language-readiness: generating new predictions by expanding the set of genes of interest
Boeckx, C. A., & Benítez‐Burraco, A. (2014) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.01324 · Cited by 65 · see citing works
The evolutionary history of genes involved in spoken and written language: beyond FOXP2
Mozzi, A., Forni, D., Clerici, M., Pozzoli, U., Mascheretti, S., Guerini, F. R., Riva, S., Bresolin, N., Cagliani, R., & Sironi, M. (2016) · Scientific Reports · doi:10.1038/srep22157 · Cited by 67 · see citing works
DISC1 as a genetic risk factor for schizophrenia and related major mental illness: response to Sullivan
Porteous, D. J., Thomson, P. A., Millar, J. K., Evans, K. L., Hennah, W., Soares, D. C., McCarthy, S., McCombie, W. R., Clapcote, S. J., Korth, C., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.160 · Cited by 66 · see citing works
The Role of the FOXP Family of Transcription Factors in ASD
Bowers, J. M., & Konopka, G. (2012) · Disease Markers · doi:10.1155/2012/456787 · Cited by 65 · see citing works
Language Impairments in ASD Resulting from a Failed Domestication of the Human Brain
Benítez‐Burraco, A., Lattanzi, W., & Murphy, E. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00373 · Cited by 61 · see citing works
The Neurodevelopmental Implications of PI3K Signaling
Waite, K., & Eickholt, B. J. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_82 · Cited by 62 · see citing works
Chromatin Decondensation by FOXP2 Promotes Human Neuron Maturation and Expression of Neurodevelopmental Disease Genes
Hickey, S. L., Berto, S., & Konopka, G. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.044 · Cited by 63 · see citing works
Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information
Maihofer, A. X., Choi, K. W., Coleman, J. R. I., Daskalakis, N. P., Denckla, C. A., Ketema, E., Morey, R. A., Polimanti, R. A., Ratanatharathorn, A. D., Torres, K., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.09.020 · Cited by 60 · see citing works
Foxp2 regulates neuronal differentiation and neuronal subtype specification
Chiu, Y.-C., Li, M., Liu, Y., Ding, J., Yu, J., & Wang, T. (2014) · Developmental Neurobiology · doi:10.1002/dneu.22166 · Cited by 61 · see citing works
Language deficits in schizophrenia and autism as related oscillatory connectomopathies: An evolutionary account
Murphy, E., & Benítez‐Burraco, A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.07.029 · Cited by 64 · see citing works
Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity
Kyrousi, C., O’Neill, A. C., Brazovskaja, A., He, Z., Kielkowski, P., Coquand, L., Giaimo, R. D., Andrea, P. D., Belka, A., Forero, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26447-w · Cited by 60 · see citing works
Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution
Mendizabal, I., Shi, L., Keller, T. E., Konopka, G., Preuss, T. M., Hsieh, T., Hu, E., Zhang, Z., Su, B., & Yi, S. V. (2016) · Molecular Biology and Evolution · doi:10.1093/molbev/msw176 · Cited by 64 · see citing works
Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions
Tsepilov, Y. A., Freidin, M. B., Shadrina, A. S., Sharapov, S., Elgaeva, E. E., Zundert, J. H. M. V., Karssen, L. C., Suri, P., Williams, F. M. K., & Aulchenko, Y. S. (2020) · Communications Biology · doi:10.1038/s42003-020-1051-9 · Cited by 62 · see citing works
New genes expressed in human brains: Implications for annotating evolving genomes
Zhang, Y. E., Landback, P., Vibranovski, M. D., & Long, M. (2012) · BioEssays · doi:10.1002/bies.201200008 · Cited by 62 · see citing works
Novel Bioinformatics Approach Identifies Transcriptional Profiles of Lineage-Specific Transposable Elements at Distinct Loci in the Human Dorsolateral Prefrontal Cortex
Guffanti, G., Bartlett, A. A., Klengel, T., Klengel, C., Hunter, R. G., Glinsky, G. V., & Macciardi, F. M. (2018) · Molecular Biology and Evolution · doi:10.1093/molbev/msy143 · Cited by 60 · see citing works
Potential role of human-specific genes, human-specific microRNAs and human-specific non-coding regulatory RNAs in the pathogenesis of Systemic Sclerosis and Sjögren's Syndrome
Jiménez, S. A., & Piera-Velázquez, S. (2013) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.04.004 · Cited by 60 · see citing works
What can mice tell us about Foxp2 function?
French, C. A., & Fisher, S. E. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.07.003 · Cited by 58 · see citing works
Sumoylation of FOXP2 Regulates Motor Function and Vocal Communication Through Purkinje Cell Development
Usui, N., Co, M., Harper, M. J., Rieger, M. A., Dougherty, J. D., & Konopka, G. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.02.008 · Cited by 58 · see citing works
Genome-Wide Analysis of a Wnt1-Regulated Transcriptional Network Implicates Neurodegenerative Pathways
Wexler, E. M., Rosen, E., Lu, D., Osborn, G. E., Martin, E., Raybould, H., & Geschwind, D. H. (2011) · Science Signaling · doi:10.1126/scisignal.2002282 · Cited by 56 · see citing works
The evolution of FOXP2 in the light of admixture
Kuhlwilm, M. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.04.006 · Cited by 56 · see citing works
Cell and transcriptomic diversity of infrapatellar fat pad during knee osteoarthritis
Peters, H., Potla, P., Rockel, J. S., Tockovska, T., Pastrello, C., Jurišica, I., Santos, K. D., Vohra, S., Fine, N. A., Lively, S. S., et al. (2024) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2024-225928 · Cited by 58 · see citing works
Foxp1 regulation of neonatal vocalizations via cortical developmentPreprint
Usui, N., Araujo, D. J., Kulkarni, A., Co, M., Ellegood, J., Harper, M. J., Toriumi, K., Lerch, J. P., & Konopka, G. (2017) · Genes & Development · doi:10.1101/gad.305037.117 · Cited by 56 · see citing works
Possible functional links among brain- and skull-related genes selected in modern humans
Benítez‐Burraco, A., & Boeckx, C. A. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.00794 · Cited by 54 · see citing works
The Archaeological Record Speaks: Bridging Anthropology and Linguistics
Balari, S., Benítez‐Burraco, A., Camps, M., Martínez, V. M. L., Lorenzo, G., & Uriagereka, J. (2011) · International Journal of Evolutionary Biology · doi:10.4061/2011/382679 · Cited by 54 · see citing works
The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2
Nazaryan, L., Stefanou, E. G., Hansen, C., Kosyakova, N., Bak, M., Sharkey, F. H., Μάντζιου, Θ., Papanastasiou, A. D., Velissariou, V., Liehr, T., et al. (2013) · European Journal of Human Genetics · doi:10.1038/ejhg.2013.147 · Cited by 53 · see citing works
The autism associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain
Peng, Y., Lu, Z.-M., Li, G., Piechowicz, M., Anderson, M. R., Uddin, Y., Wu, J., & Qiu, S.-F. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.182 · Cited by 49 · see citing works
Implicit Artificial Syntax Processing: Genes, Preference, and Bounded Recursion
Folia, V., Forkstam, C., Ingvar, M., & Petersson, K. M. (2011) · Biolinguistics · doi:10.5964/bioling.8835 · Cited by 52 · see citing works
miRNA regulatory variation in human evolution
Li, J., & Zhang, Z. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.10.008 · Cited by 52 · see citing works

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

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

Human-specific transcriptional regulation of CNS development genes by FOXP2

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks