Affinage

FOXP2

Forkhead box protein P2 · UniProt O15409

Length
715 aa
Mass
79.9 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXP2 is a forkhead-domain transcription factor that functions as both a transcriptional repressor and activator to orchestrate neural circuit development, synaptic plasticity, and motor-skill learning across cortico-striatal, thalamic, and cerebellar circuits. Its forkhead domain drives DNA binding and can form a domain-swapped dimer enabled by a proline-to-alanine substitution unique to the FOXP subfamily, while the leucine zipper mediates coiled-coil dimerization that also contributes to DNA binding; FOXP2 heterodimerizes with FOXP1 and FOXP4 to differentially regulate target genes (PMID:16407075, PMID:30887622, PMID:25027557). In the striatum, FOXP2 directly represses MEF2C to control corticostriatal synaptogenesis and spine density, and its loss shifts excitatory/inhibitory balance by upregulating GAD67 and increasing GABAergic transmission in medium spiny neurons; in Purkinje cells, FOXP2 restrains intrinsic excitability, and its loss impairs spike modulation during movement (PMID:27595386, PMID:30187194, PMID:30108312). FOXP2 is post-translationally regulated by SUMOylation at K674 (mediated by PIAS1/PIAS3 and reversed by SENP2), which modulates its transcriptional output on targets including DISC1 and SRPX2, and is required in vivo for Purkinje cell dendritic arborization and vocal communication (PMID:26867680, PMID:27009683, PMID:26212494).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2006 High

    The atomic structure of the FOXP2 forkhead domain revealed how it binds DNA and how the FOXP subfamily uniquely domain-swaps to dimerize, mapping disease-causing mutations to either the DNA-contact or dimer interface and establishing the structural basis of FOXP2 dysfunction.

    Evidence X-ray crystallography at 1.9 Å resolution of FOXP2 forkhead domain–DNA complex

    PMID:16407075

    Open questions at the time
    • Structure covers only the forkhead domain; full-length FOXP2 structure with leucine zipper and zinc finger remains unsolved
    • Domain-swapped dimer relevance in vivo not directly tested
  2. 2007 High

    Genome-wide identification of FOXP2-bound promoters in neuron-like cells established that FOXP2 functions as both a transcriptional repressor and activator, resolving whether it acts solely as a repressor and revealing a broad target gene repertoire confirmed in embryonic mouse brain.

    Evidence ChIP-chip in SH-SY5Y cells with in vivo validation in mouse embryonic brain, luciferase reporter assays

    PMID:17999362

    Open questions at the time
    • Mechanism distinguishing activator vs. repressor mode at specific loci unknown
    • Cofactors mediating dual transcriptional activity not identified in this study
  3. 2007 High

    Demonstration that Foxp2 and Foxp1 cooperatively regulate lung and esophageal development, with T1alpha as a direct shared target, established that FOXP2 functions outside the nervous system and that FOXP family members interact genetically.

    Evidence Conditional mouse knockouts with double-mutant genetic epistasis analysis

    PMID:17428829

    Open questions at the time
    • Whether FOXP2 lung function requires heterodimerization with FOXP1 at the protein level was not tested
    • Full spectrum of non-neural FOXP2 targets undefined
  4. 2010 High

    Direct binding of FOXP2 to SRPX2 and uPAR promoters, abolished by the R553H mutation and partially impaired by a leucine-zipper mutation (M406T), linked FOXP2 transcriptional repression to specific epilepsy/language-associated gene targets and implicated the leucine zipper in target selectivity.

    Evidence EMSA gel-shift assays showing direct DNA binding, luciferase reporter assays with disease mutations

    PMID:20858596

    Open questions at the time
    • In vivo relevance of SRPX2/uPAR repression by FOXP2 in neural circuits not demonstrated
    • Whether M406T affects dimerization specifically was not resolved
  5. 2011 High

    In vivo electrophysiology in R552H knockin mice revealed that FOXP2 is essential for normal striatal dynamics during motor-skill learning, shifting the understanding from a static developmental role to an active role in circuit-level plasticity.

    Evidence Single-unit recordings in dorsolateral striatum of awake behaving R552H knockin mice during motor-skill learning

    PMID:21876543

    Open questions at the time
    • Molecular targets mediating the altered striatal plasticity were not identified
    • Whether the firing-rate phenotype reflects cell-autonomous vs. circuit-level dysfunction was unresolved
  6. 2013 High

    Discovery that Foxp2 protein levels are sexually dimorphic in neonatal rat brain and that in vivo knockdown eliminates sex differences in ultrasonic vocalizations directly implicated FOXP2 dosage in sex-differentiated vocal communication.

    Evidence Western blot quantification of Foxp2 across brain regions, in vivo siRNA knockdown with vocalization recording

    PMID:23426656

    Open questions at the time
    • Upstream mechanism driving sexually dimorphic FOXP2 expression not defined
    • Whether androgen receptor directly regulates Foxp2 transcription was addressed subsequently but remained incomplete
  7. 2016 High

    Identification of MEF2C as a direct FOXP2 target whose de-repression drives the synaptogenesis and vocalization deficits in Foxp2 mutants established a key epistatic pathway: FOXP2 represses MEF2C to permit corticostriatal spine formation and vocal output.

    Evidence ChIP for direct binding, conditional KO, intrastriatal viral rescue of Mef2c, genetic epistasis in mice

    PMID:27595386

    Open questions at the time
    • Whether MEF2C mediates all or only part of the FOXP2-dependent striatal phenotype unclear
    • Downstream effectors of MEF2C in this pathway not identified
  8. 2016 High

    Biochemical characterization of FOXP2 SUMOylation at K674 by PIAS1 and PIAS3, reversed by SENP2, with the R553H disease mutation reducing modification, established a post-translational regulatory axis; in vivo, cerebellar SUMOylation by PIAS3 was shown to be required for Purkinje cell dendritic morphology and vocalization.

    Evidence Co-IP identification of PIAS1/PIAS3 as E3 ligases, site-directed mutagenesis, in utero electroporation in cerebellum, behavioral assays

    PMID:26212494 PMID:26867680 PMID:27009683

    Open questions at the time
    • Functional consequence of SUMOylation on specific chromatin targets or cofactor recruitment unknown
    • Whether SUMOylation functions in striatum similarly to cerebellum untested
  9. 2018 High

    Region-specific conditional knockouts dissected FOXP2's circuit-specific roles: Purkinje cell deletion increased intrinsic excitability and disrupted spike modulation during movement, while striatal deletion altered sequence variability, resolving whether FOXP2 acts cell-autonomously in distinct motor circuits.

    Evidence Purkinje cell-, striatum-, and cortex-specific Cre-mediated knockouts with in vivo electrophysiology and operant behavior

    PMID:30108312

    Open questions at the time
    • Ion channels or conductances regulated by FOXP2 in Purkinje cells not identified
    • How cortical FOXP2 loss produces its distinct behavioral phenotype mechanistically unexplored
  10. 2019 High

    Biophysical domain dissection resolved the respective contributions of the leucine zipper (dimerization and DNA binding), zinc finger (dimerization only), and forkhead domain (primary DNA-binding determinant), providing a quantitative architecture for FOXP2 function.

    Evidence Single-molecule mass photometry and electrically switchable DNA biochips with domain deletions/mutations

    PMID:30887622

    Open questions at the time
    • How dimerization state influences target selectivity genome-wide not determined
    • Heterodimer stoichiometry with FOXP1/FOXP4 not measured biophysically
  11. 2019 High

    Genome-wide chromatin accessibility and transcriptomic analyses during human neuronal differentiation revealed that FOXP2 represses proliferation genes via direct DNA binding but activates neuronal maturation genes indirectly through cofactors NFIA/NFIB, resolving how one factor can simultaneously repress and activate distinct gene programs.

    Evidence ATAC-seq, RNA-seq, loss-of-function and DNA-binding-domain mutants in differentiating human neurons

    PMID:31067457

    Open questions at the time
    • Mechanism by which FOXP2 activates genes without direct DNA contact (e.g., tethered via NFI factors) not structurally resolved
    • Whether this dual mode operates in vivo in developing human cortex untested
  12. 2021 High

    Discovery that FOXP2 is a flow-induced transcription factor in lymphatic endothelial cells downstream of FOXC2, required for collecting lymphatic vessel valve morphogenesis via NFATc1, expanded FOXP2's function beyond neurons to mechanosensitive vascular biology.

    Evidence Two independent conditional endothelial KO mouse lines (Tie2-Cre, Prox1-CreERT2), in vitro shear stress on primary LECs

    PMID:33934370

    Open questions at the time
    • Direct transcriptional targets of FOXP2 in lymphatic endothelium not comprehensively mapped
    • Whether SUMOylation modulates FOXP2 function in this non-neural context unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how SUMOylation and cofactor interactions (NFIA/NFIB, CTBP, FOXA2) are integrated to switch FOXP2 between repressor and activator modes at specific loci, and what ion channels or synaptic molecules FOXP2 controls in Purkinje cells to regulate intrinsic excitability.
  • No structural model of full-length FOXP2 or FOXP2–cofactor complexes
  • Direct transcriptional targets controlling Purkinje cell intrinsic excitability unidentified
  • Whether human-specific FOXP2 amino acid changes alter cofactor recruitment or SUMOylation remains unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-112316 Neuronal System 4 R-HSA-1266738 Developmental Biology 4
Partners
ARFOXA2FOXP1FOXP4NFIANFIBPIAS1PIAS3

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Crystal structure of the FOXP2 forkhead domain bound to DNA at 1.9 Å resolution revealed that FOXP2 binds DNA through its forkhead domain, can form a domain-swapped dimer enabled by substitution of a conserved proline with alanine in the FOXP subfamily, and that disease-causing mutations map to either the DNA-binding surface or the domain-swapping dimer interface. X-ray crystallography (1.9 Å crystal structure) with functional mapping of disease mutations Structure High 16407075
2007 ChIP-chip in human neuron-like cells identified genomic sites directly bound by FOXP2 protein; altered FOXP2 levels changed expression of target genes; FOXP2 has dual functionality, acting as both a transcriptional repressor and activator at occupied promoters. In vivo Foxp2-chromatin interactions in embryonic mouse brain were confirmed for a subset of targets. Chromatin immunoprecipitation coupled with promoter microarrays (ChIP-chip), luciferase reporter assays, quantitative gene expression in cell and mouse models American journal of human genetics High 17999362
2007 Foxp2 and Foxp1 cooperatively regulate lung alveolarization and esophageal muscle development; T1alpha (a lung alveolar type 1 cell gene) is a direct transcriptional target of both Foxp2 and Foxp1; loss of Foxp2 combined with haploinsufficiency of Foxp1 severely worsens lung and esophageal phenotypes, demonstrating functional cooperativity. Conditional mouse knockout, in vitro and in vivo transcriptional assays, genetic epistasis (double mutant analysis) Development High 17428829
2016 In mouse striatum, Foxp2 directly binds to the Mef2c promoter and transcriptionally represses it; Foxp2-mediated suppression of Mef2c controls corticostriatal synaptogenesis and spinogenesis; Foxp2 deletion de-represses Mef2c, and reducing Mef2c (intrastriatally or globally) rescues vocalization deficits and striatal spinogenesis in Foxp2-deletion mutants. In vivo mouse genetics (conditional knockout, rescue experiments), ChIP (direct DNA binding), intrastriatal virus-mediated gene knockdown, genetic epistasis Nature neuroscience High 27595386
2011 Mice carrying the KE-family R552H Foxp2 mutation show abnormally high ongoing striatal activity and dramatically altered striatal plasticity during motor-skill learning, with most neurons showing negative rather than positive modulation of firing rate, demonstrating that FOXP2 is critical for striatal circuit function in vivo. In vivo electrophysiology in awake-behaving mice (KE-family point-mutation knockin), motor-skill learning paradigm Molecular psychiatry High 21876543
2010 FOXP2 directly binds to promoter regions of SRPX2 and uPAR (identified by gel retardation assays) and represses their transcription; the disease-causing FOXP2 p.R553H mutation abolishes binding to these promoters; a novel FOXP2 mutation (p.M406T) in the leucine-zipper domain partially impairs SRPX2 but not uPAR regulation. Gel retardation (EMSA) assays, luciferase reporter assays, transfection in cell lines, mutation analysis Human molecular genetics High 20858596
2011 FOXP2 directly binds to the 5' regulatory region of MET and overexpression of FOXP2 results in transcriptional repression of MET in human neuronal progenitor cells. Chromatin immunoprecipitation, overexpression in human neuronal progenitor cells, gene expression assays The Journal of neuroscience High 21832174
2016 FOXP2 is post-translationally modified by SUMOylation at lysine K674 (K673 in mice); PIAS1 promotes this modification; the disease-causing R553H mutation markedly reduces SUMOylation; K674 is conserved across all vertebrate FOXP2 orthologues and FOXP1/4 paralogues. SUMOylation does not detectably alter subcellular localization, stability, dimerization or transcriptional repression in cellular assays. Biochemical co-immunoprecipitation, site-directed mutagenesis, cellular assays for localization/stability/dimerization/transcription Scientific reports High 26867680
2016 FOXP2 sumoylation at K674 (K673 in mice) is mediated by PIAS3 as E3 ligase in the neonatal mouse cerebellum; sumoylation modifies transcriptional regulation by FOXP2; cerebellar FOXP2 sumoylation is required for Purkinje cell dendritic arborization and for normal motor function and vocal communication in mice. In vitro co-immunoprecipitation, in vivo colocalization, in utero electroporation, behavioral assays in mice Biological psychiatry High 27009683
2016 Heterozygous loss of Foxp2 in mice decreases excitatory (AMPA-mediated) currents and increases inhibitory (GABA-mediated) currents in D1+ medium spiny neurons of striatum; reduced Foxp2 increases GAD67 expression leading to increased presynaptic GABA content and release; pharmacological blockade of inhibitory activity in vivo partially rescues motor-skill learning deficits. Whole-cell patch clamp in brain slices, western blot for GAD67, pharmacological rescue in behaving mice Brain structure & function High 30187194
2012 FOXP2 inhibits DISC1 promoter activity and DISC1 protein expression; this inhibition is diminished by two FOXP2 point mutations (R553H and R328X) that cause developmental verbal dyspraxia. Dual luciferase reporter assays, western blot for DISC1 protein, FOXP2 point-mutation analysis Human molecular genetics Medium 22434823
2014 FOXP1, FOXP2, and FOXP4 form homo- and heterodimers; specific combinations of FOXP1/2/4 dimers differentially regulate transcription of FOXP2 target genes (including CER1, SFRP4, WISP2, PRICKLE1, NCOR2, SNW1, NEUROD2, PAX3, EFNB3, SLIT1). Stable transfection in HEK293 cells, real-time PCR for target gene expression Journal of molecular neuroscience Medium 25027557
2019 FOXP2 represses proliferation-promoting genes in a DNA-binding-dependent manner during human neuronal differentiation; FOXP2 and its cofactors NFIA and NFIB activate neuronal maturation genes without requiring direct FOXP2-DNA contact; FOXP2 and NFI cofactors drive chromatin accessibility changes associated with maturation of excitatory cortical neurons. Genome-wide ATAC-seq (chromatin accessibility), RNA-seq, loss-of-function in differentiating human neurons, comparison with human fetal brain data Cell reports High 31067457
2016 Rare FOXP2 variants showed that an identified CTBP-binding region exists in the N-terminal portion of FOXP2; the two human-lineage amino acid substitutions in this region did not detectably alter CTBP binding; FOXP2 variants with reduced polyglutamine tracts did not show altered behavior in cellular assays, indicating polyglutamine tracts are non-essential for core FOXP2 function. Co-immunoprecipitation, luciferase transcriptional reporter assays, localization assays in cell models, dimerization assays Journal of neurodevelopmental disorders Medium 27933109
2019 The leucine zipper domain of FOXP2 mediates dimerization via coiled-coil formation and also contributes to DNA binding; the zinc finger contributes to protein dimerization when the leucine zipper coiled-coil is intact but is not involved in DNA binding; the forkhead domain is the key driver of DNA binding. Electrically switchable DNA biochips, single-molecule mass photometry, biochemical domain deletion/mutation analysis Angewandte Chemie High 30887622
2014 Foxp2 promotes neuronal differentiation in embryonic forebrain neural progenitors without affecting proliferation or survival; induces expression of PDGFRα which mediates its neurogenic effect; positively regulates medium spiny neuron differentiation from lateral ganglionic eminence while negatively regulating interneuron formation from dorsal medial ganglionic eminence through interaction with the Sonic hedgehog pathway. Primary neural progenitor culture, gain/loss-of-function, gene expression analysis, epistasis with Shh pathway Developmental neurobiology Medium 24453072
2017 Foxp2 regulates thalamic nuclear identity and thalamocortical projection patterns during development; in Foxp2(R552H) knockin mice, posterior thalamic nuclei are shrunken while intermediate region nuclei are expanded, and thalamocortical projection patterns are correspondingly altered. Foxp2(R552H) knockin mice, anatomical analysis of thalamic nuclei, tract-tracing of thalamocortical projections Cerebral cortex Medium 27384060
2018 Selective Foxp2 disruption in cerebellar Purkinje cells increases simple spike firing rate and decreases modulation of firing during limb movements due to increased intrinsic excitability (not altered excitatory or inhibitory inputs), resulting in slowed lever pressing and skilled locomotion deficits. Striatal Foxp2 disruption affects variability of lever-press sequences, while cortical disruption has distinct effects. Region-specific conditional knockout (Purkinje cell-, striatum-, cortex-specific Cre lines), operant behavior, in vivo Purkinje cell electrophysiology Molecular psychiatry High 30108312
2013 Foxp2 protein levels are significantly higher in multiple developing brain regions of male rat pups compared to females; siRNA-mediated knockdown of Foxp2 in brain eliminates sex differences in ultrasonic vocalizations and alters order of dam retrieval of pups, directly implicating Foxp2 in sex-differentiated vocal communication. Western blot for Foxp2 protein, siRNA knockdown in vivo, ultrasonic vocalization recording and analysis The Journal of neuroscience High 23426656
2014 Androgen receptor protein physically interacts with Foxp2 (co-immunoprecipitation and immunofluorescence), and dihydrotestosterone (DHT) alters both Foxp2 and Foxp1 mRNA and protein levels in striatum, cerebellar vermis, and cortex, suggesting androgens are upstream regulators of Foxp2 expression. Co-immunoprecipitation, immunofluorescence, DHT treatment of cell cultures, western blot, mRNA quantification Endocrinology Medium 25247470
2008 FoxP2 protein is acutely downregulated in zebra finch Area X (striatal nucleus) when adult males sing; this downregulation differs from mRNA regulation patterns and is not attributable to corticosterone stress response. Western blot for FoxP2 protein in brain regions across different singing contexts, corticosterone measurement Journal of neurophysiology Medium 18701760
2008 Lef1 (a Wnt signaling transcription factor) regulates foxP2 expression in specific CNS domains; Lef1 directly binds to foxP2 enhancer regions (foxP2-enhancerA.1 and foxP2-enhancerB) as confirmed by chromatin immunoprecipitation; loss of lef1 abolishes foxP2 expression in tectum, mid-hindbrain boundary, and hindbrain. Loss-of-function (morpholino knockdown), ChIP, in vivo enhancer-GFP reporter assays in zebrafish BMC developmental biology Medium 18950487
2021 FOXP2 expression in lymphatic endothelial cells is induced by shear stress/lymph flow and is downstream of FOXC2; genetic deletion of Foxp2 in endothelial cells results in enlarged collecting lymphatic vessels and defective valves with loss of NFATc1 activity, identifying FOXP2 as a flow-induced transcriptional regulator of lymphatic vessel morphogenesis. Conditional endothelial knockout mice (Tie2-Cre; Prox1-CreERT2), in vitro shear stress on primary LECs, transcriptional analysis The EMBO journal High 33934370
2021 foxp2 zebrafish loss-of-function mutants show increased locomotor activity; foxp2 is expressed in GABAergic neurons in brain motor regions; genetic or pharmacological disruption of Gad1 or GABA-A receptors phenocopies foxp2 mutant hyperactivity; GABA-A receptor agonist (muscimol) rescues the hyperactive foxp2 mutant phenotype, establishing that foxp2 regulates locomotor activity via GABAergic signaling. CRISPR/Cas9 knockout zebrafish, behavioral assays, pharmacological rescue, genetic interaction with gad1b Translational psychiatry Medium 34650032
2019 Cortical-specific homozygous Foxp2 deletion in mice causes abnormal social approach behavior and altered ultrasonic vocalizations; cortical pyramidal neurons show aberrant regulation of social-behavior-related genes including downregulation of Mint2/Apba2. Conditional cortical knockout mice, unbiased behavioral profiling, cell-type-specific transcriptomics Human molecular genetics Medium 30357341
2021 FOXP2 interacts with FOXA2 (identified by mass spectrometry on FOXA2 pulldowns, confirmed by co-IP); FOXP2 activates transcription of E-cadherin and PHF2 in concert with FOXA2, acting in this context as a transcriptional activator; this activity inhibits epithelial-mesenchymal transition in breast cancer cells. Mass spectrometry pulldown, co-immunoprecipitation, ChIP, luciferase reporter assays, in vivo metastasis assay Frontiers in oncology Medium 33718155
2018 Mapping of human FOXP2 enhancers by chromatin conformation capture (3C) identified long-range promoter-interacting regions; FOXP family members and TBR1 regulate FOXP2 promoter and enhancer activity, indicating FOXP2 is subject to autoregulatory and cross-regulatory control. Chromatin conformation capture (3C), luciferase reporter assays for enhancer activity, transcription factor overexpression Frontiers in molecular neuroscience Medium 29515369
2016 SUMOylation of FOXP2 at K674 modulates its transcriptional activity towards downstream target genes DISC1, SRPX2, and MiR200c; SENP2 (a SUMO protease) significantly decreases FOXP2 SUMOylation; the disease-causing R553H mutation reduces SUMOylation potential; acidic residues downstream of the core SUMO motif are required for full SUMOylation. In vivo SUMOylation assay, site-directed mutagenesis, reporter gene transcriptional assays, SENP2 knockdown Journal of cellular biochemistry Medium 26212494

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Molecular evolution of FOXP2, a gene involved in speech and language. Nature 717 12192408
2009 FOXP2 as a molecular window into speech and language. Trends in genetics : TIG 334 19304338
2005 Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits. American journal of human genetics 282 15877281
2005 FOXP2 and the neuroanatomy of speech and language. Nature reviews. Neuroscience 264 15685218
2003 FOXP2 expression during brain development coincides with adult sites of pathology in a severe speech and language disorder. Brain : a journal of neurology 249 12876151
2004 FoxP2 expression in avian vocal learners and non-learners. The Journal of neuroscience : the official journal of the Society for Neuroscience 247 15056696
2007 Foxp2 and Foxp1 cooperatively regulate lung and esophagus development. Development (Cambridge, England) 236 17428829
2003 Language fMRI abnormalities associated with FOXP2 gene mutation. Nature neuroscience 202 14555953
2007 High-throughput analysis of promoter occupancy reveals direct neural targets of FOXP2, a gene mutated in speech and language disorders. American journal of human genetics 184 17999362
2006 Structure of the forkhead domain of FOXP2 bound to DNA. Structure (London, England : 1993) 170 16407075
2002 Accelerated protein evolution and origins of human-specific features: Foxp2 as an example. Genetics 156 12524352
2002 FOXP2 is not a major susceptibility gene for autism or specific language impairment. American journal of human genetics 150 11894222
2014 MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell stem cell 147 25515522
2000 The SPCH1 region on human 7q31: genomic characterization of the critical interval and localization of translocations associated with speech and language disorder. American journal of human genetics 116 10880297
2012 The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders. Human genetics 108 22736078
2011 FOXP2 and the role of cortico-basal ganglia circuits in speech and language evolution. Current opinion in neurobiology 104 21592779
2013 Foxp2 mediates sex differences in ultrasonic vocalization by rat pups and directs order of maternal retrieval. The Journal of neuroscience : the official journal of the Society for Neuroscience 97 23426656
2006 Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2. American journal of medical genetics. Part A 94 16470794
2016 Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c. Nature neuroscience 92 27595386
2011 An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning. Molecular psychiatry 88 21876543
2009 Conservation and diversity of Foxp2 expression in muroid rodents: functional implications. The Journal of comparative neurology 87 18972576
2011 Regulation of MET by FOXP2, genes implicated in higher cognitive dysfunction and autism risk. The Journal of neuroscience : the official journal of the Society for Neuroscience 81 21832174
2010 Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex. Human molecular genetics 80 20858596
2007 Generation of mice with a conditional Foxp2 null allele. Genesis (New York, N.Y. : 2000) 76 17619227
2008 Birdsong decreases protein levels of FoxP2, a molecule required for human speech. Journal of neurophysiology 72 18701760
2010 The structure of innate vocalizations in Foxp2-deficient mouse pups. Genes, brain, and behavior 71 20132318
2002 Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues. Mechanisms of development 70 14516685
2011 Evo-devo, deep homology and FoxP2: implications for the evolution of speech and language. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 69 21690130
2007 Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review. American journal of medical genetics. Part A 68 17330859
2002 FOXP2: novel exons, splice variants, and CAG repeat length stability. Human genetics 63 12189486
2018 No Evidence for Recent Selection at FOXP2 among Diverse Human Populations. Cell 62 30078708
2016 FOXP2 variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum. Journal of medical genetics 60 27572252
2003 FOXP2 in focus: what can genes tell us about speech and language? Trends in cognitive sciences 58 12804692
2005 An evolutionary perspective on FoxP2: strictly for the birds? Current opinion in neurobiology 56 16266802
2008 The timing of selection at the human FOXP2 gene. Molecular biology and evolution 55 18413354
2004 Association between the FOXP2 gene and autistic disorder in Chinese population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 54 15108192
2014 Foxp2 regulates neuronal differentiation and neuronal subtype specification. Developmental neurobiology 53 24453072
2019 Chromatin Decondensation by FOXP2 Promotes Human Neuron Maturation and Expression of Neurodevelopmental Disease Genes. Cell reports 52 31067457
2014 Transcriptional regulation by FOXP1, FOXP2, and FOXP4 dimerization. Journal of molecular neuroscience : MN 52 25027557
2005 Molecular cloning and developmental expression of foxP2 in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 51 16028276
2016 Knockout of Foxp2 disrupts vocal development in mice. Scientific reports 49 26980647
2014 What can mice tell us about Foxp2 function? Current opinion in neurobiology 48 25048596
2016 MicroRNA-190 regulates FOXP2 genes in human gastric cancer. OncoTargets and therapy 47 27382302
2008 Domain-specific regulation of foxP2 CNS expression by lef1. BMC developmental biology 44 18950487
2016 Sumoylation of FOXP2 Regulates Motor Function and Vocal Communication Through Purkinje Cell Development. Biological psychiatry 42 27009683
2013 miR-9 and miR-140-5p target FoxP2 and are regulated as a function of the social context of singing behavior in zebra finches. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 24133256
2003 Mutation screening of FOXP2 in individuals diagnosed with autistic disorder. American journal of medical genetics. Part A 40 12655497
2007 Recruitment of FoxP2-expressing neurons to area X varies during song development. Developmental neurobiology 39 17443826
2016 The language-related transcription factor FOXP2 is post-translationally modified with small ubiquitin-like modifiers. Scientific reports 37 26867680
2015 Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 26142732
2013 Young and intense: FoxP2 immunoreactivity in Area X varies with age, song stereotypy, and singing in male zebra finches. Frontiers in neural circuits 36 23450800
2019 Altered social behavior in mice carrying a cortical Foxp2 deletion. Human molecular genetics 35 30357341
2019 FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis. eLife 35 31099752
2017 Equivalent missense variant in the FOXP2 and FOXP1 transcription factors causes distinct neurodevelopmental disorders. Human mutation 35 28741757
2017 The FOXP2-Driven Network in Developmental Disorders and Neurodegeneration. Frontiers in cellular neuroscience 35 28798667
2018 Differential effects of Foxp2 disruption in distinct motor circuits. Molecular psychiatry 34 30108312
2002 Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues. Gene expression patterns : GEP 33 12617805
2014 Monoallelic expression of the human FOXP2 speech gene. Proceedings of the National Academy of Sciences of the United States of America 32 25422445
2012 The DISC1 promoter: characterization and regulation by FOXP2. Human molecular genetics 32 22434823
2012 Fos-activation of FoxP2 and Lmx1b neurons in the parabrachial nucleus evoked by hypotension and hypertension in conscious rats. Neuroscience 32 22641087
2004 FoxP2 in song-learning birds and vocal-learning mammals. The Journal of heredity 32 15618302
2017 miR-618 Inhibits Prostate Cancer Migration and Invasion by Targeting FOXP2. Journal of Cancer 31 28900488
2014 Androgen modulation of Foxp1 and Foxp2 in the developing rat brain: impact on sex specific vocalization. Endocrinology 31 25247470
2010 Aberrant expression of the neuronal transcription factor FOXP2 in neoplastic plasma cells. British journal of haematology 31 20096010
2015 Differential coexpression of FoxP1, FoxP2, and FoxP4 in the Zebra Finch (Taeniopygia guttata) song system. The Journal of comparative neurology 30 25556631
2010 The speech and language FOXP2 gene modulates the phenotype of frontotemporal lobar degeneration. Journal of Alzheimer's disease : JAD 30 20858950
2009 Characterization of Foxp2-expressing cells in the developing spinal cord. Neuroscience 30 19463901
2009 Language features in a mother and daughter of a chromosome 7;13 translocation involving FOXP2. Journal of speech, language, and hearing research : JSLHR 30 19797137
2022 The novel role of circular RNA ST3GAL6 on blocking gastric cancer malignant behaviours through autophagy regulated by the FOXP2/MET/mTOR axis. Clinical and translational medicine 29 35061934
2018 MiR-34a Regulates Axonal Growth of Dorsal Root Ganglia Neurons by Targeting FOXP2 and VAT1 in Postnatal and Adult Mouse. Molecular neurobiology 29 29637443
2021 FOXA2-Interacting FOXP2 Prevents Epithelial-Mesenchymal Transition of Breast Cancer Cells by Stimulating E-Cadherin and PHF2 Transcription. Frontiers in oncology 28 33718155
2019 lncRNA XIST attenuates hypoxia-induced H9c2 cardiomyocyte injury by targeting the miR-122-5p/FOXP2 axis. Molecular and cellular probes 27 31887421
2018 Downregulation of FOXP2 promotes breast cancer migration and invasion through TGFβ/SMAD signaling pathway. Oncology letters 27 29805593
2018 Foxp2 regulates anatomical features that may be relevant for vocal behaviors and bipedal locomotion. Proceedings of the National Academy of Sciences of the United States of America 27 30104377
2017 Foxp2 Regulates Identities and Projection Patterns of Thalamic Nuclei During Development. Cerebral cortex (New York, N.Y. : 1991) 27 27384060
2016 The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation. Journal of cellular biochemistry 27 26212494
2021 Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels. The EMBO journal 26 33934370
2019 Differential Song Deficits after Lentivirus-Mediated Knockdown of FoxP1, FoxP2, or FoxP4 in Area X of Juvenile Zebra Finches. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 31641053
2016 Early neuroimaging markers of FOXP2 intragenic deletion. Scientific reports 26 27734906
2011 Genetic variation in FOXP2 alters grey matter concentrations in schizophrenia patients. Neuroscience letters 26 21334420
2006 Expression of FoxP2 during zebrafish development and in the adult brain. The International journal of developmental biology 26 16525940
2020 The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2. Cancers 25 31936744
2017 microRNA‑196b promotes cell migration and invasion by targeting FOXP2 in hepatocellular carcinoma. Oncology reports 24 29207173
2019 Dissecting FOXP2 Oligomerization and DNA Binding. Angewandte Chemie (International ed. in English) 23 30887622
2013 FOXP2. Wiley interdisciplinary reviews. Cognitive science 23 24765219
2021 Increased locomotor activity via regulation of GABAergic signalling in foxp2 mutant zebrafish-implications for neurodevelopmental disorders. Translational psychiatry 22 34650032
2018 The untold stories of the speech gene, the FOXP2 cancer gene. Genes & cancer 22 29725501
2016 Expression of forkhead box transcription factor genes Foxp1 and Foxp2 during jaw development. Gene expression patterns : GEP 22 26969076
2016 Functional characterization of rare FOXP2 variants in neurodevelopmental disorder. Journal of neurodevelopmental disorders 22 27933109
2014 Specific expression of FOXP2 in cerebellum improves ultrasonic vocalization in heterozygous but not in homozygous Foxp2 (R552H) knock-in pups. Neuroscience letters 22 24607928
2010 Association between FOXP2 gene and speech sound disorder in Chinese population. Psychiatry and clinical neurosciences 22 20923434
2019 Downregulation of miR-222-3p Reverses Doxorubicin-Resistance in LoVo Cells Through Upregulating Forkhead Box Protein P2 (FOXP2) Protein. Medical science monitor : international medical journal of experimental and clinical research 21 30904920
2019 LncRNA TSLNC8 inhibits proliferation of breast cancer cell through the miR-214-3p/FOXP2 axis. European review for medical and pharmacological sciences 20 31646574
2018 Mapping of Human FOXP2 Enhancers Reveals Complex Regulation. Frontiers in molecular neuroscience 20 29515369
2018 Foxp2 loss of function increases striatal direct pathway inhibition via increased GABA release. Brain structure & function 20 30187194
2015 A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice. Genes, brain, and behavior 20 26250064
2008 Multiple transcription start sites for FOXP2 with varying cellular specificities. Gene 20 18316164
2005 No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population. Neuroscience research 20 15998549
2022 miR-134-5p promotes inflammation and apoptosis of trophoblast cells via regulating FOXP2 transcription in gestational diabetes mellitus. Bioengineered 19 34969354
2019 Beyond Critical Period Learning: Striatal FoxP2 Affects the Active Maintenance of Learned Vocalizations in Adulthood. eNeuro 19 31001575