Affinage

FOXG1

Forkhead box protein G1 · UniProt P55316

Length
489 aa
Mass
52.4 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXG1 is a winged-helix forkhead transcription factor that acts as a master regulator of telencephalic cell fate, neurogenesis, and neuronal differentiation, functioning predominantly as a DNA-binding transcriptional repressor (PMID:14704420, PMID:33058871). Its DNA-binding domain adopts a winged-helix fold with a distinctive two-β-strand wing2 architecture, and disease-causing mutations within it compromise DNA binding and/or thermal stability (PMID:33058871). FOXG1 represses cell fate programs to enforce cortical identity: it continuously suppresses Cajal-Retzius cell fate in progenitors (PMID:14704420), restrains GABAergic interneuron overproduction in a dosage-dependent manner (PMID:26186191, PMID:30804331), and inhibits gliogenesis while promoting neurogenesis (PMID:20506244). It executes repression by partnering with Groucho/TLE family co-repressors via N-terminal eh1 and C-terminal motifs (PMID:20356955, PMID:12660810) and with the zinc-finger factor Rp58, the FOXG1-Rp58 complex directly binding and repressing the migration/axon-guidance genes Robo1, Slit3, and Reelin (PMID:30392794). FOXG1 promotes progenitor proliferation and blocks cell-cycle exit by binding the SMAD/FOXO complex to inhibit TGFβ/FOXO-driven transcription of Cdkn1a (p21) and by antagonizing GDF11 negative-feedback signaling during neurogenesis (PMID:19297409, PMID:27224923). Dynamic FOXG1 expression governs cortical neuron migration, with downregulation triggering Unc5D and the multipolar phase and re-expression required for cortical plate entry (PMID:22726835). FOXG1 also supports postmitotic neuron survival downstream of IGF-1/Akt signaling, requiring Akt phosphorylation at Thr271 and intact DNA-binding capacity (PMID:21228151). Beyond canonical nuclear repression, a membrane-potential-dependent mitochondrial pool controls bioenergetics and differentiation (PMID:26508630), and FOXG1 regulates miR200 biogenesis by associating with DDX5/p68 and the DROSHA microprocessor (PMID:30539330). In non-neural and oncogenic contexts FOXG1 cooperates with SOX2 to maintain glioblastoma stem cells by repressing Foxo3 (PMID:28465359), forms TLE1 repression complexes restraining NOTCH regulators (PMID:29316219), and acts as a corepressor of androgen receptor and of AIB1 (PMID:17482455, PMID:23660594).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2004 High

    Whether FOXG1 actively suppresses an early neuronal fate or whether that competence is simply lost during development was unresolved; this established FOXG1 as a continuous repressor of Cajal-Retzius cell fate in cortical progenitors.

    Evidence Foxg1 null and conditional inducible knockout in cortical progenitors with cell-fate marker analysis

    PMID:14704420

    Open questions at the time
    • Direct DNA targets mediating Cajal-Retzius repression not identified
    • Co-repressor requirement for this specific fate decision not defined
  2. 2007 Medium

    FOXG1's molecular role outside neural development was unknown; this identified it as a corepressor of androgen receptor through C-terminal protein interaction.

    Evidence Yeast two-hybrid screen with pull-down, mammalian two-hybrid, and reporter assays

    PMID:17482455

    Open questions at the time
    • Physiological context of AR corepression not established
    • Single-lab interaction without in vivo validation
  3. 2009 High

    The pathway through which FOXG1 controls neurogenesis was unclear; genetic epistasis placed it upstream of TGFβ/GDF11 negative-feedback signaling rather than Fgf8.

    Evidence Foxg1/Gdf11 double-mutant epistasis with gene-dosage rescue in olfactory epithelium

    PMID:19297409

    Open questions at the time
    • Whether FOXG1 directly represses Gdf11/follistatin transcription not shown
    • Generalizability beyond olfactory epithelium untested at this stage
  4. 2010 High

    The biochemical basis of FOXG1 repression was undefined; this mapped a bipartite eh1/YWPMSPF interaction with TLE2 required for ventral telencephalon specification.

    Evidence Xenopus neurogenesis assay, binding-motif mutagenesis, and morpholino knockdown

    PMID:20356955

    Open questions at the time
    • Genome-wide targets of the FOXG1-TLE2 complex not defined
    • Other TLE family members' roles not delineated
  5. 2011 High

    Whether Akt signaling routes through FOXG1 to control neuronal survival was unknown; this showed Thr271 phosphorylation by Akt and DNA binding are required for FOXG1's survival function downstream of IGF-1.

    Evidence Site-directed mutagenesis (Asp219, Thr271), pharmacological Akt inhibition, and dominant-negative approaches in cerebellar granule neurons

    PMID:21228151

    Open questions at the time
    • Survival target genes regulated downstream not identified
    • Whether phosphorylation alters localization or DNA binding not resolved here
  6. 2011 Medium

    The chromatin behavior of FOXG1 and how disease mutations perturb it were unknown; FRAP revealed reversibly and irreversibly bound chromatin populations altered by truncating mutations.

    Evidence FRAP of GFP-FoxG1 comparing wild-type and disease-associated mutant dynamics in live cells

    PMID:22091895

    Open questions at the time
    • Molecular identity of the irreversibly bound fraction unknown
    • Relationship between binding kinetics and transcriptional output not established
  7. 2012 High

    How dynamic FOXG1 levels orchestrate migration was unclear; this showed FOXG1 downregulation induces Unc5D and the multipolar phase while re-expression is needed for cortical plate entry.

    Evidence Conditional genetic manipulation, in utero electroporation, and migration/marker analysis

    PMID:22726835

    Open questions at the time
    • Mechanism timing FOXG1 down- and up-regulation not defined
    • Direct versus indirect control of Unc5D not established
  8. 2012 High

    How brain size is constrained relative to FOXG1 was unknown; this identified the chromatin remodeler Snf2l as an antagonist that limits Foxg1 expression and progenitor expansion.

    Evidence Snf2l mutant mice with Foxg1 dosage-reduction rescue and ChIP at the Foxg1 locus

    PMID:22516202

    Open questions at the time
    • Mechanism of Snf2l repression at the Foxg1 locus not detailed
    • Whether this loop operates in human progenitors untested
  9. 2015 High

    Whether FOXG1 dysregulation drives GABAergic imbalance in human disease was unknown; organoid RNAi rescue placed FOXG1 overexpression upstream of inhibitory neuron overproduction in ASD.

    Evidence iPSC-derived 3D neural organoids with FOXG1 RNAi rescue and transcriptomic network analysis

    PMID:26186191

    Open questions at the time
    • Direct targets driving GABAergic fate not identified
    • Causal mutation underlying FOXG1 overexpression in patients not defined
  10. 2015 High

    A non-nuclear function for FOXG1 was unsuspected; this demonstrated a membrane-potential-dependent mitochondrial pool with domain-specific control of fission/fusion and differentiation.

    Evidence Subcellular fractionation, mitochondrial import assays with isolated mitochondria, and deletion mapping

    PMID:26508630

    Open questions at the time
    • Mitochondrial molecular targets of FOXG1 unknown
    • How nuclear/mitochondrial partitioning is regulated not established
  11. 2015 High

    How activating AKT3 mutations cause migration defects was unclear; FOXG1 was identified as the downstream effector that represses Reelin, with derepression causing non-cell-autonomous defects.

    Evidence In utero electroporation of AKT3(E17K), human FMCD tissue, and pharmacological rescue

    PMID:26523971

    Open questions at the time
    • Direct biochemical link between AKT3 activity and FOXG1 repression of Reelin not fully resolved
    • Whether Thr271 phosphorylation mediates this not tested here
  12. 2016 Medium

    How FOXG1 prevents premature cell-cycle exit was unknown; this showed FOXG1 binds the SMAD/FOXO complex to inhibit Cdkn1a (p21) transcription.

    Evidence Overexpression/knockdown in cortical progenitors, reporter assays, and RNA-seq

    PMID:27224923

    Open questions at the time
    • Stoichiometry and structure of the FOXG1-SMAD-FOXO complex not defined
    • Single-lab evidence
  13. 2017 High

    How FOXG1 maintains a proliferative stem state in glioblastoma was unclear; this showed FOXG1/SOX2 cooperatively repress Foxo3 via a shared cis-element to restrict astrocyte differentiation.

    Evidence CRISPR deletion, in vivo transplantation, ChIP, RNA-seq, and methylation profiling

    PMID:28465359

    Open questions at the time
    • Whether SOX2 cooperation operates in normal neurogenesis not addressed
    • Direct versus indirect regulation of epigenetic target genes unresolved
  14. 2017 Medium

    FOXG1's role in interneuron migration was undefined; conditional deletion identified it as an upstream regulator of Dlx1/2, Mash1, Prox1 and guidance receptors.

    Evidence Dlx5/6-Cre conditional KO with migration assays and expression analysis

    PMID:26620267

    Open questions at the time
    • Direct versus indirect target relationships not separated
    • Single-lab study
  15. 2018 High

    The complex repressing callosal guidance genes was unknown; this identified a FOXG1-Rp58 complex directly repressing Robo1, Slit3, and Reelin, with single-allele loss causing callosal agenesis.

    Evidence Neuron-specific conditional KO, ChIP, co-IP, reporter assays, and phenotypic analysis

    PMID:30392794

    Open questions at the time
    • Whether Rp58 partnership extends to other FOXG1 targets unknown
    • Mechanism of Rp58 recruitment not defined
  16. 2018 High

    A post-transcriptional role for FOXG1 was unsuspected; this showed FOXG1 associates with DDX5/p68 and DROSHA to regulate miR200 biogenesis and PRKAR2B/PKA signaling.

    Evidence Reciprocal co-IP, small RNA-seq, quantitative proteomics, and in vivo RNA-seq

    PMID:30539330

    Open questions at the time
    • Whether microprocessor association is independent of transcriptional function unresolved
    • Breadth of FOXG1-dependent miRNAs beyond miR200 not defined
  17. 2018 Medium

    FOXG1's genome-wide repression program in GBM was unmapped; ChIP-Seq identified FOXG1:TLE1 complexes repressing NOTCH regulators to maintain stem cell properties.

    Evidence ChIP-Seq and RNA-Seq in patient-derived brain tumor-initiating cells

    PMID:29316219

    Open questions at the time
    • No functional rescue confirming target dependence
    • Single-lab study
  18. 2018 Medium

    FOXG1's role in cochlear hair cell development was unknown; conditional KO produced an extra hair cell row via Notch inhibition followed by apoptosis through loss of Wnt/IGF/EGF signaling.

    Evidence HC-specific conditional KO with ABR testing and RNA-Seq

    PMID:30336149

    Open questions at the time
    • Direct FOXG1 targets in hair cells not identified
    • Single-lab study
  19. 2019 Medium

    Whether FOXG1 controls neuronal morphology was unclear; overexpression stimulated dendrite elongation via Hes1-pCreb1 with PKA/AKT dependence and reduced PP1/PP2A activity.

    Evidence In vivo/in vitro overexpression with pharmacological PKA/AKT inhibition and phosphatase assays

    PMID:29385539

    Open questions at the time
    • Whether Hes1 is a direct FOXG1 target not established
    • Loss-of-function confirmation absent
  20. 2019 High

    FOXG1's postnatal interneuron function was undefined; conditional deletion placed it upstream of Dlx1-Pak3 controlling dendritic complexity and migration, with rescue confirming the pathway.

    Evidence Gad2-CreER conditional KO with Dlx1 overexpression and Pak3 knockdown rescue

    PMID:29912324

    Open questions at the time
    • Direct regulation of Dlx1 by FOXG1 not biochemically shown
    • Seizure phenotype mechanism not fully linked
  21. 2019 Medium

    How FOXG1 dosage scales with interneuron output was unknown; precise endogenous dosage control showed threshold effects on MGE-derived neuron production.

    Evidence CRISPR + SMASh dosage control in hPSCs with neural differentiation assays

    PMID:30804331

    Open questions at the time
    • Mechanistic basis of dose thresholds at target genes not defined
    • Single-lab study
  22. 2020 High

    The structural basis of FOXG1 DNA recognition and of disease mutations was unknown; the 1.6 Å DBD-DNA structure revealed a distinctive winged-helix fold and explained how mutations impair binding or stability.

    Evidence X-ray crystallography with mutational and thermal-stability validation

    PMID:33058871

    Open questions at the time
    • Full-length FOXG1 and co-repressor-bound structures not determined
    • How wing2 architecture sets target specificity in vivo untested
  23. 2021 Medium

    Whether FOXG1 protects sensory cells via autophagy was unknown; this showed FOXG1 promotes hair cell survival by activating autophagy and reducing ROS, with aspirin acting upstream.

    Evidence Knockdown/overexpression in cochlear hair cells with autophagy, ROS, and apoptosis assays plus an aging mouse model

    PMID:34006186

    Open questions at the time
    • Direct autophagy gene targets in this context not mapped
    • Single-lab study
  24. 2022 Medium

    How viral insult disrupts FOXG1 was unknown; ZIKV infection caused C-terminal-dependent nuclear displacement and downregulation, with Thr271 implicated in apoptosis protection.

    Evidence ZIKV infection of human neural progenitors with deletion mapping and growth-factor treatment

    PMID:35714598

    Open questions at the time
    • Mechanism linking ZIKV to FOXG1 relocalization not defined
    • Whether nuclear displacement causes the differentiation phenotype unresolved
  25. 2023 Medium

    FOXG1's control of hippocampal-subicular neuron identity was undefined; this showed FOXG1 represses Zbtb20/Prox1/Epha4 and activates Nr4a2 to specify RSC and subiculum neuron fates.

    Evidence Postmitotic conditional KO with single-cell RNA-seq and target identification

    PMID:36791184

    Open questions at the time
    • Co-factors mediating these fate decisions not identified
    • Single-lab study
  26. 2023 Medium

    How astrocyte autophagy/neuroinflammation is gated was unclear; CB2R activation was shown to block FOXG1 binding at the MAP1LC3B promoter, boosting autophagy and NLRP3 degradation.

    Evidence CUT&RUN, transcriptomics, in vivo knockdown, and astrocyte culture in a Parkinson's model

    PMID:38110963

    Open questions at the time
    • Mechanism by which CB2R signaling displaces FOXG1 from chromatin not defined
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FOXG1 selects between repression and activation, partitions between nucleus and mitochondria, and integrates phosphorylation, co-repressor recruitment, and target specificity into context-specific fate decisions remains unresolved.
  • No structure of full-length FOXG1 or co-repressor complexes
  • Signals governing nuclear/mitochondrial partitioning unknown
  • Rules determining activator versus repressor mode at individual targets undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 2 GO:0000228 nuclear chromosome 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 2 R-HSA-8953854 Metabolism of RNA 1
Partners
ARDDX5DROSHANCOA3RP58SOX2TLE1TLE2
Complex memberships
DDX5/DROSHA microprocessor associationFOXG1-Rp58 complexFOXG1-SMAD/FOXO complexFOXG1-TLE co-repressor complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Foxg1 constitutively suppresses Cajal-Retzius cell fate in cortical progenitors. In Foxg1 null mutants, an excess of Cajal-Retzius neurons is produced; conditional inactivation of Foxg1 in deep-layer cortical progenitors demonstrates that Foxg1 is continuously required to suppress this earliest-born neuron fate, establishing that the competence to generate Cajal-Retzius cells is actively repressed rather than lost during later cortical development. Foxg1 null mutant analysis and conditional (inducible) Foxg1 knockout in cortical progenitors; cell-fate marker analysis Science High 14704420
2012 FoxG1 expression is dynamically regulated during cortical neuron migration in the intermediate zone. Downregulation of FoxG1 at the onset of the multipolar cell phase induces Unc5D expression, determining laminar identity; subsequent re-expression of FoxG1 is required for cells to exit the multipolar phase and enter the cortical plate. Conditional genetic strategies (in vivo Foxg1 manipulation), in utero electroporation, cell migration and marker analysis Neuron High 22726835
2015 Overexpression of FOXG1 in ASD-derived brain organoids is responsible for overproduction of GABAergic inhibitory neurons. RNAi knockdown of FOXG1 in ASD organoids rescues the excess GABAergic neuron production, placing FOXG1 upstream of GABAergic neuron fate specification. iPSC-derived 3D neural organoids, RNA interference (RNAi) knockdown of FOXG1, transcriptome and gene network analysis Cell High 26186191
2010 FoxG1 interacts with TLE2 (a Groucho/TLE family co-repressor) via an N-terminal eh1 motif and a C-terminal YWPMSPF motif to regulate ventral telencephalon specification. Mutation of either binding motif abolishes functional cooperation with TLE2, and knockdown of either FoxG1 or TLE2 disrupts ventral telencephalon development. Xenopus ectopic neurogenesis assay, binding domain mutagenesis, morpholino knockdown, co-expression studies Development High 20356955
2015 A fraction of Foxg1 localizes within mitochondria in a membrane potential-dependent manner; amino acids 277–302 are critical for mitochondrial localization. Full-length Foxg1 overexpression enhances mitochondrial membrane potential and promotes fission and mitosis, whereas the C-terminal fragment (aa 272–481), which localizes selectively to the mitochondrial matrix, promotes organelle fusion and early neuronal differentiation. Subcellular fractionation, live-cell imaging, mitochondrial import assay with isolated mitochondria, deletion mutagenesis, functional assays (ΔΨm, fission/fusion, differentiation) Proceedings of the National Academy of Sciences of the United States of America High 26508630
2009 Foxg1 promotes olfactory neurogenesis by antagonizing GDF11-mediated negative-feedback signaling. Gdf11 mutations rescue major neurogenesis defects in Foxg1−/− olfactory epithelium in a gene-dosage-dependent manner; loss of follistatin (a GDF11 antagonist) in Foxg1−/− tissue contributes to the phenotype. Foxg1 promotes neurogenesis in the olfactory epithelium through inhibition of TGFβ/Gdf11 signaling rather than through Fgf8 upregulation. Genetic epistasis (Foxg1/Gdf11 double mutants), in vivo gene expression analysis, compound heterozygous rescue Development High 19297409
2011 FoxG1 promotes survival of postmitotic neurons via an Akt-dependent mechanism. Thr271 phosphorylation by Akt is required for FoxG1's survival-promoting effect; pharmacological Akt inhibition blocks wild-type FoxG1 survival function but not phosphomimetic T271 mutants. The first 36 N-terminal residues and DNA-binding ability (Asp219) are also required. FoxG1 acts downstream of IGF-1/Akt signaling to maintain neuronal survival. Ectopic expression and knockdown in cerebellar granule neurons, site-directed mutagenesis (Asp219, Thr271), pharmacological Akt inhibition, IGF-1 treatment, dominant-negative FoxG1 The Journal of neuroscience High 21228151
2018 Foxg1 forms a transcription complex with Rp58 in pyramidal neurons. The Foxg1-Rp58 complex directly binds and represses Robo1, Slit3, and Reelin genes, key regulators of callosal axon guidance and neuronal migration. Inactivation of a single Foxg1 allele specifically in cortical neurons is sufficient to cause cortical hypoplasia and corpus callosum agenesis. Conditional KO (neuron-specific), ChIP (chromatin immunoprecipitation), co-immunoprecipitation, transcriptional reporter assays, in vivo phenotypic analysis Neuron High 30392794
2020 Crystal structure of the FOXG1 DNA-binding domain (DBD) in complex with the forkhead consensus DNA site DBE2 was determined at 1.6 Å resolution. FOXG1-DBD adopts a winged helix fold; the N terminus, H3 helix and wing2 region show distinct DNA recognition compared to other FOX family members. Wing2 forms a unique two-β-strand architecture. Disease-causing mutations in the DBD affect DNA binding, protein thermal stability, or both. X-ray crystallography (1.6 Å), mutagenesis of disease-associated variants, thermal stability assays, DNA-binding assays Journal of molecular biology High 33058871
2015 In focal malformations of cortical development (FMCD), activated AKT3(E17K) derepresses reelin transcription through FOXG1, causing non-cell-autonomous neuronal migration defects in neighboring cells. FOXG1 is identified as a downstream effector of AKT3 that normally represses Reelin. Treatments targeting AKT signaling or inactivating reelin restored migration. In utero electroporation of FMCD-causing mutation into mouse brain, human FMCD tissue analysis, epistasis/rescue experiments with pathway inhibitors Nature medicine High 26523971
2012 Snf2l (a chromatin remodeler) antagonizes Foxg1 to regulate brain size. Snf2l mutant mice show forebrain hypercellularity due to increased Foxg1 expression and enhanced progenitor expansion; reducing Foxg1 dosage rescues this phenotype. Snf2l binds the Foxg1 locus at midneurogenesis. Snf2l mutant mouse analysis, Foxg1 dosage reduction rescue, ChIP for Snf2l binding at Foxg1 locus, cell proliferation assays Developmental cell High 22516202
2017 In glioblastoma, FOXG1 and SOX2 cooperatively restrict astrocyte differentiation and maintain a proliferative neural stem cell state. FOXG1 transcriptionally represses Foxo3 through a conserved FOXG1/SOX2-bound cis-regulatory element; FOXG1-null GBM cells transplanted in vivo show increased astrocyte differentiation and upregulate FOXO3. Transcriptional targets include cell cycle regulators (Plk1, Mycn) and epigenetic regulators (Dnmt1, Dnmt3b, Tet3). CRISPR/Cas9 deletion, in vivo transplantation, ChIP, RNA-seq, DNA methylation profiling Genes & development High 28465359
2016 FOXG1 binds the SMAD/FOXO protein complex and prevents cell cycle exit by inhibiting FOXO- and TGFβ-mediated transcription of Cdkn1a (p21). FOXG1 also transcriptionally regulates Foxo1, Foxo3, Kcnh3, TGFβ ligands, and IGF family ligands during telencephalic development; in mature neurons FOXG1 activates Kcnh3 transcription. Overexpression and knockdown in cortical progenitors, transcriptional reporter assays, pharmacological IGF1 pathway inhibition, RNA-seq Oncotarget Medium 27224923
2018 FOXG1 regulates PRKAR2B expression both transcriptionally and posttranscriptionally via miR200b/a/429. FOXG1 affects miR200 biogenesis by associating with the RNA helicase DDX5/p68 and the microprocessor complex (DROSHA); DDX5 recruits FOXG1 to DROSHA. Loss of FOXG1 leads to reduced miR200 and elevated PRKAR2B, which attenuates PKA activity. Genome-wide small RNA-seq, quantitative proteomics, co-immunoprecipitation (FOXG1–DDX5–DROSHA), RNA-seq of Foxg1cre/+ hippocampi, N2a cell overexpression Molecular neurobiology High 30539330
2007 FoxG1 functions as a corepressor of the androgen receptor (AR). The C-terminal region of FoxG1 (aa 175–489) interacts with AR (aa 325–919) identified in a yeast two-hybrid screen and validated by pull-down and mammalian two-hybrid assays. Full-length FoxG1 strongly represses AR-mediated transactivation. Yeast two-hybrid screen, pull-down assay, mammalian two-hybrid assay, transcriptional reporter assay The Journal of steroid biochemistry and molecular biology Medium 17482455
2010 Foxg1 inhibits gliogenesis and promotes neuronogenesis in cortical progenitors through distinct mechanisms from Emx2; Foxg1 also dramatically stimulates neurite outgrowth in these cells. Lentiviral overexpression in embryonic cortical progenitors, multiplex cytofluorometry, immunocytofluorescence with cell-type-specific reporters Stem cells Medium 20506244
2011 FoxG1 (Qin) binds TLE1 (a Groucho family co-repressor) via a 60-amino-acid stretch C-terminal to its winged-helix DNA-binding domain, inducing TLE1 phosphorylation. Binding of TLE1 enhances Qin-mediated transformation of chicken embryo fibroblasts; adding the TLE1-binding WRPW motif to a transformation-defective Qin mutant restores binding and transformation. Yeast two-hybrid screen, mammalian two-hybrid assay, co-expression transformation assays in chicken embryo fibroblasts, domain deletion mapping Oncogene Medium 12660810
2019 Foxg1 overexpression in neocortical pyramidal neurons stimulates dendrite elongation via upregulation of Hes1, which in turn upregulates pCreb1 (pro-dendritogenic) and downregulates Syt and Ndr1 (antagonists of dendrite elongation). Foxg1-driven pCreb1 upregulation requires PKA and AKT and correlates with reduced PP1 and PP2A phosphatase activity. In vivo and in vitro Foxg1 overexpression, Hes1 pathway analysis, pharmacological inhibition of PKA and AKT, phosphatase activity assays Cerebral cortex Medium 29385539
2013 FoxG1 transcriptionally represses AIB1 by binding to the AIB1 gene promoter region responsible for AIB1 autostimulation, displacing the activating complex (AIB1, E2F1, SP1). FoxG1 overexpression suppresses endogenous AIB1 mRNA and protein and induces apoptosis in MCF-7 breast cancer cells that is partially rescued by AIB1 overexpression. FoxG1 was identified as an AIB1-interacting protein. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), transient overexpression, siRNA-mediated knockdown, apoptosis assays Molecular endocrinology Medium 23660594
2008 Foxg1 is required cell-autonomously for production of mature olfactory receptor neurons. In Foxg1 knockout mice, olfactory progenitors show defects in both proliferation and differentiation; mosaic analysis in zebrafish demonstrates the cell-autonomous requirement. Foxg1 is also required for development of the olfactory bulb and vomeronasal organs. Foxg1 knockout mouse analysis, antisense morpholino knockdown in zebrafish, mosaic analysis in zebrafish, BrdU proliferation assays, cell-type marker analysis The Journal of neuroscience High 18480279
2021 FOXG1 promotes survival of cochlear hair cells through regulation of autophagy. Inhibition of FOXG1 decreases autophagy activity, leading to ROS accumulation and apoptosis. Aspirin increases FOXG1 expression, which activates autophagy, reduces ROS, and inhibits apoptosis in mimetic aging hair cells. FOXG1 knockdown and overexpression in cochlear hair cells and OC-1 cells, autophagy assays (LC3, bafilomycin), ROS measurement, apoptosis assays, in vivo mouse aging model Autophagy Medium 34006186
2018 Foxg1 conditional knockout in postnatal cochlear hair cells results in an extra row of hair cells via Notch signaling inhibition followed by subsequent apoptosis of HCs through inhibition of Wnt, IGF, and EGF signaling pathways. Conditional KO (HC-specific), auditory brainstem response testing, RNA-Seq, qPCR validation, histological analysis Neuropharmacology Medium 30336149
2017 Conditional disruption of Foxg1 in interneurons (Dlx5/6-Cre) results in migration defects associated with downregulation of Robo1, EphA4, and CXCR4/7 receptors, and upregulation of Dlx1/2, Mash1, and Prox1. Foxg1 acts as an upstream regulator of Dlx1/2, Mash1, and Prox1 to control interneuron development. Conditional KO (Dlx5/6-Cre × Foxg1fl/fl), in vitro migration assays, mRNA and protein expression analysis, neurite morphology analysis Cerebral cortex Medium 26620267
2019 Foxg1 in postnatal interneurons functions upstream of the Dlx1–Pak3 signaling pathway to regulate dendritic complexity and migration. Conditional deletion (Gad2-CreER) impairs somatostatin-, calretinin-, and NPY-positive interneuron distributions. Overexpression of Dlx1 or knockdown of Pak3 rescues differentiation defects, placing Foxg1 upstream of Dlx1-Pak3 in postnatal interneuron development. Conditional KO (Gad2-CreER × Foxg1fl/fl), Dlx1 overexpression rescue, Pak3 siRNA knockdown, interneuron marker analysis, seizure susceptibility assays Cerebral cortex High 29912324
2011 GFP-FoxG1 fusion protein associates with chromatin in two populations: a reversibly bound majority and an irreversibly bound fraction. Disease-associated FoxG1 mutations (p.Gln46X, p.Tyr400X) dramatically alter chromatin binding kinetics and reduce the irreversibly bound fraction compared to severe-phenotype mutant (Ser323fsX325) and wild-type protein. Fluorescence recovery after photobleaching (FRAP) of GFP-FoxG1 in live cells, comparison of wild-type and mutant protein dynamics Clinical genetics Medium 22091895
2018 FOXG1 and TLE1 form transcriptional repression complexes in glioblastoma-initiating cells. ChIP-Seq identified 150 direct FOXG1 targets, several shared with TLE1, including negative regulators of NOTCH signaling (e.g., CHAC1). FOXG1:TLE1 complexes repress NOTCH pathway regulators to maintain GBM stem cell properties. ChIP-Seq, RNA-Seq in patient-derived brain tumor-initiating cells Molecular oncology Medium 29316219
2022 Zika virus infection induces nuclear displacement and downregulation of FOXG1 in human neural progenitor cells. The Thr271 residue in the AKT phosphorylation domain of FOXG1 is involved in apoptosis protection; the C-terminal region (residues 428–481) is critical for the nuclear displacement phenotype. EGF and FGF2 growth factors also participate in FOXG1 nuclear localization. ZIKV infection of human neural progenitor cells and other cell models, FOXG1 deletion mapping, AKT domain mutation, growth factor treatment, cell cycle and apoptosis assays, subcellular localization imaging Stem cell reports Medium 35714598
2023 FOXG1 transcriptionally represses Zbtb20, Prox1, and Epha4 to prevent CA3-PyN and DG-GC identities during specification of RSC pyramidal neurons and subiculum neurons; FOXG1 directly activates Nr4a2 to promote subiculum pyramidal neuron identity. TBR1, controlled by FOXG1 during CA1-PyN specification, is downregulated in the absence of FOXG1. Postmitotic FOXG1 conditional KO, single-cell RNA-seq, transcriptional regulation assays, identification of direct FOXG1 target genes Science advances Medium 36791184
2003 Excess FoxG1 (via retroviral overexpression) causes overgrowth of the neural tube by suppressing apoptosis rather than increasing proliferation. A DNA-binding-defective form of FoxG1 does not produce these effects, indicating that FoxG1's function as a transcriptional repressor (requiring DNA binding) mediates this anti-apoptotic effect. Retroviral overexpression in chicken embryo neural tube, DNA-binding domain mutagenesis, BrdU proliferation assay, TUNEL apoptosis assay Journal of neurobiology Medium 14608667
2023 CB2R activation in astrocytes inhibits FOXG1 binding to the MAP1LC3B autophagy gene promoter, increases autophagy, and promotes NLRP3 degradation via the autophagy-lysosome pathway, reducing neuroinflammation in a Parkinson's disease model. CUT&RUN confirmed FOXG1 binding at MAP1LC3B in astrocytes. CUT&RUN chromatin profiling, transcriptomic sequencing, in vivo adenoviral knockdown, in vitro astrocyte culture, ELISA, western blot Journal of neuroinflammation Medium 38110963
2019 FOXG1 dosage dose-dependently affects GABAergic interneuron development in human pluripotent stem cell-derived neurons; 60% FOXG1 expression mildly affects GABAergic interneuron development while 30% expression thresholds production of MGE-derived neurons. CRISPR/Cas9 + SMASh technology for precise endogenous protein dosage control in hPSCs, neural differentiation assays, interneuron marker analysis Nature communications Medium 30804331

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders. Cell 833 26186191
2004 Foxg1 suppresses early cortical cell fate. Science (New York, N.Y.) 317 14704420
2004 PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. Nature immunology 293 14985713
2000 Transcriptional repression by blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase. Molecular and cellular biology 273 10713181
1999 PRDI-BF1/Blimp-1 repression is mediated by corepressors of the Groucho family of proteins. Genes & development 227 9887105
1995 Schnurri is required for Drosophila Dpp signaling and encodes a zinc finger protein similar to the mammalian transcription factor PRDII-BF1. Cell 178 7774018
2008 MicroRNA-9 modulates Cajal-Retzius cell differentiation by suppressing Foxg1 expression in mouse medial pallium. The Journal of neuroscience : the official journal of the Society for Neuroscience 165 18842901
2006 Foxg1 is required for morphogenesis and histogenesis of the mammalian inner ear. Developmental dynamics : an official publication of the American Association of Anatomists 155 16691564
2011 Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains. Molecular cell 151 22099305
2012 Dynamic FoxG1 expression coordinates the integration of multipolar pyramidal neuron precursors into the cortical plate. Neuron 128 22726835
2021 FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway. Autophagy 121 34006186
2012 Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies. Epilepsia 120 22998673
2015 An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development. Nature medicine 100 26523971
2015 VEGF-Mediated Induction of PRD1-BF1/Blimp1 Expression Sensitizes Tumor Vasculature to Oncolytic Virus Infection. Cancer cell 97 26212250
2017 Elevated FOXG1 and SOX2 in glioblastoma enforces neural stem cell identity through transcriptional control of cell cycle and epigenetic regulators. Genes & development 96 28465359
1992 Only two of the five zinc fingers of the eukaryotic transcriptional repressor PRDI-BF1 are required for sequence-specific DNA binding. Molecular and cellular biology 94 1569931
2010 Emx2 and Foxg1 inhibit gliogenesis and promote neuronogenesis. Stem cells (Dayton, Ohio) 89 20506244
2008 Foxg1 is required for development of the vertebrate olfactory system. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 18480279
2017 FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants. Genetics in medicine : official journal of the American College of Medical Genetics 79 28661489
2011 FoxG1 promotes the survival of postmitotic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 77 21228151
2018 FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical Connections. Neuron 76 30392794
2007 Different evolutionary histories of the two classical class I genes BF1 and BF2 illustrate drift and selection within the stable MHC haplotypes of chickens. Journal of immunology (Baltimore, Md. : 1950) 69 17442958
2007 Disruption of Foxg1 expression by knock-in of cre recombinase: effects on the development of the mouse telencephalon. Neuroscience 68 17640820
2018 The role of FOXG1 in the postnatal development and survival of mouse cochlear hair cells. Neuropharmacology 67 30336149
2009 Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11. Development (Cambridge, England) 67 19297409
2020 Transcription and Beyond: Delineating FOXG1 Function in Cortical Development and Disorders. Frontiers in cellular neuroscience 66 32158381
2011 FOXG1-Related Disorders: From Clinical Description to Molecular Genetics. Molecular syndromology 65 22670136
2017 Evolutionary conservation and conversion of Foxg1 function in brain development. Development, growth & differentiation 60 28581027
2006 Immunization-induced perturbation of human blood plasma cell pool: progressive maturation, IL-6 responsiveness, and high PRDI-BF1/BLIMP1 expression are critical distinctions between antigen-specific and nonspecific plasma cells. Journal of immunology (Baltimore, Md. : 1950) 60 16547239
2018 Delineating FOXG1 syndrome: From congenital microcephaly to hyperkinetic encephalopathy. Neurology. Genetics 57 30533527
2014 Epilepsy and outcome in FOXG1-related disorders. Epilepsia 55 24836831
2012 Snf2l regulates Foxg1-dependent progenitor cell expansion in the developing brain. Developmental cell 55 22516202
1991 HIV-EP2, a new member of the gene family encoding the human immunodeficiency virus type 1 enhancer-binding protein. Comparison with HIV-EP1/PRDII-BF1/MBP-1. The Journal of biological chemistry 55 2022670
2015 Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics. Proceedings of the National Academy of Sciences of the United States of America 54 26508630
2010 FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation. Development (Cambridge, England) 54 20356955
2019 FOXG1 Dose in Brain Development. Frontiers in pediatrics 52 31824897
2015 The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system. Molecular and cellular neurosciences 50 25937343
2023 A network pharmacology approach and experimental validation to investigate the anticancer mechanism of Qi-Qin-Hu-Chang formula against colitis-associated colorectal cancer through induction of apoptosis via JNK/p38 MAPK signaling pathway. Journal of ethnopharmacology 47 37852337
2016 The FOXG1/FOXO/SMAD network balances proliferation and differentiation of cortical progenitors and activates Kcnh3 expression in mature neurons. Oncotarget 47 27224923
2003 Excess FoxG1 causes overgrowth of the neural tube. Journal of neurobiology 43 14608667
2016 MiR-200b promotes the cell proliferation and metastasis of cervical cancer by inhibiting FOXG1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38 27044840
2010 A FOXG1 mutation in a boy with congenital variant of Rett syndrome. Neurogenetics 38 20734096
2019 Precisely controlling endogenous protein dosage in hPSCs and derivatives to model FOXG1 syndrome. Nature communications 37 30804331
1996 The B-lymphocyte maturation promoting transcription factor BLIMP1/PRDI-BF1 maps to D6S447 on human chromosome 6q21-q22.1 and the syntenic region of mouse chromosome 10. Genomics 36 8921366
1992 Regulation of human immunodeficiency virus enhancer function by PRDII-BF1 and c-rel gene products. Journal of virology 36 1727488
2016 Visual impairment in FOXG1-mutated individuals and mice. Neuroscience 34 27001178
2015 The hyperkinetic movement disorder of FOXG1-related epileptic-dyskinetic encephalopathy. Developmental medicine and child neurology 34 26344814
2007 FOXG1 is overexpressed in hepatoblastoma. Human pathology 34 17217994
2018 Two class I genes of the chicken MHC have different functions: BF1 is recognized by NK cells while BF2 is recognized by CTLs. Immunogenetics 32 29947944
2014 Cloning and expression of ophB gene encoding organophosphorus hydrolase from endophytic Pseudomonas sp. BF1-3 degrades organophosphorus pesticide chlorpyrifos. Ecotoxicology and environmental safety 32 25062445
2016 Generation and analysis of an improved Foxg1-IRES-Cre driver mouse line. Developmental biology 31 26896590
2014 The facial neural crest controls fore- and midbrain patterning by regulating Foxg1 expression through Smad1 activity. Development (Cambridge, England) 30 24917504
2023 Targeting CB2R in astrocytes for Parkinson's disease therapy: unraveling the Foxg1-mediated neuroprotective mechanism through autophagy-mediated NLRP3 degradation. Journal of neuroinflammation 29 38110963
2003 Binding of the corepressor TLE1 to Qin enhances Qin-mediated transformation of chicken embryo fibroblasts. Oncogene 29 12660810
1995 Avian cellular homolog of the qin oncogene. Proceedings of the National Academy of Sciences of the United States of America 29 7831308
2017 Impaired Interneuron Development after Foxg1 Disruption. Cerebral cortex (New York, N.Y. : 1991) 28 26620267
2019 Foxg1 Regulates the Postnatal Development of Cortical Interneurons. Cerebral cortex (New York, N.Y. : 1991) 27 29912324
2019 Disruption of Foxg1 impairs neural plasticity leading to social and cognitive behavioral defects. Molecular brain 26 31253171
2018 Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells. Molecular oncology 26 29316219
2018 MiR-378 promotes the cell proliferation of non-small cell lung cancer by inhibiting FOXG1. European review for medical and pharmacological sciences 26 29509249
2020 Cyanidin-related antidepressant-like efficacy requires PI3K/AKT/FoxG1/FGF-2 pathway modulated enhancement of neuronal differentiation and dendritic maturation. Phytomedicine : international journal of phytotherapy and phytopharmacology 25 32593103
2019 Baicalin exerts antidepressant effects through Akt/FOXG1 pathway promoting neuronal differentiation and survival. Life sciences 25 30794828
2018 FOXG1 Expression Is Elevated in Glioma and Inhibits Glioma Cell Apoptosis. Journal of Cancer 25 29581755
2018 FoxG1 facilitates proliferation and inhibits differentiation by downregulating FoxO/Smad signaling in glioblastoma. Biochemical and biophysical research communications 25 30172378
2011 Expanding the phenotype associated with FOXG1 mutations and in vivo FoxG1 chromatin-binding dynamics. Clinical genetics 25 22091895
2009 Distinct expression of two foxg1 paralogues in zebrafish. Gene expression patterns : GEP 25 19379839
2020 Structural Basis for DNA Recognition by FOXG1 and the Characterization of Disease-causing FOXG1 Mutations. Journal of molecular biology 24 33058871
2019 Foxg1 Overexpression in Neocortical Pyramids Stimulates Dendrite Elongation Via Hes1 and pCreb1 Upregulation. Cerebral cortex (New York, N.Y. : 1991) 23 29385539
2017 Impaired vitreous composition and retinal pigment epithelium function in the FoxG1::LRP2 myopic mice. Biochimica et biophysica acta. Molecular basis of disease 23 28366874
2020 Conditional Deletion of Foxg1 Alleviates Demyelination and Facilitates Remyelination via the Wnt Signaling Pathway in Cuprizone-Induced Demyelinated Mice. Neuroscience bulletin 22 33015737
2018 FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus. Molecular neurobiology 21 30539330
2010 Characterization and frequency of a newly identified HIV-1 BF1 intersubtype circulating recombinant form in São Paulo, Brazil. Virology journal 21 20398371
2017 Collagen-derived dipeptide prolyl-hydroxyproline promotes osteogenic differentiation through Foxg1. Cellular & molecular biology letters 19 29213293
2007 FoxG1, a member of the forkhead family, is a corepressor of the androgen receptor. The Journal of steroid biochemistry and molecular biology 19 17482455
2019 Foxg1 Antagonizes Neocortical Stem Cell Progression to Astrogenesis. Cerebral cortex (New York, N.Y. : 1991) 18 30821834
2009 The chicken BF1 (classical MHC class I) gene shows evidence of selection for diversity in expression and in promoter and signal peptide regions. Immunogenetics 18 19212763
2023 FOXG1 drives transcriptomic networks to specify principal neuron subtypes during the development of the medial pallium. Science advances 17 36791184
2018 Foxg1 deletion impairs the development of the epithalamus. Molecular brain 17 29394901
2017 Characterization of HIV-1 CRF90_BF1 and putative novel CRFs_BF1 in Central West, North and Northeast Brazilian regions. PloS one 17 28628667
2016 Spindle-E cycling between nuage and cytoplasm is controlled by Qin and PIWI proteins. The Journal of cell biology 17 27091448
2016 RNA activation of haploinsufficient Foxg1 gene in murine neocortex. Scientific reports 17 27995975
2014 Epilepsy in patients with duplications of chromosome 14 harboring FOXG1. Pediatric neurology 17 24731847
2010 Longitudinal analysis of HIV-1 BF1 recombinant strains in vertically infected children from Argentina reveals a decrease in CRF12_BF pol gene mosaic patterns and high diversity of BF unique recombinant forms. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 17 21130901
1991 Localization of the zinc finger DNA-binding protein HIV-EP1/MBP-1/PRDII-BF1 to human chromosome 6p22.3-p24. Genomics 17 2037300
2015 Familial recurrences of FOXG1-related disorder: Evidence for mosaicism. American journal of medical genetics. Part A 16 26364767
2013 A 2.0 Mb microdeletion in proximal chromosome 14q12, involving regulatory elements of FOXG1, with the coding region of FOXG1 being unaffected, results in severe developmental delay, microcephaly, and hypoplasia of the corpus callosum. European journal of medical genetics 16 23895774
2023 Elevated FOXG1 in glioblastoma stem cells cooperates with Wnt/β-catenin to induce exit from quiescence. Cell reports 15 37243590
2022 FOXG1 as a Potential Therapeutic Target for Alzheimer's Disease with a Particular Focus on Cell Cycle Regulation. Journal of Alzheimer's disease : JAD 15 35180113
2022 FOXG1 Contributes Adult Hippocampal Neurogenesis in Mice. International journal of molecular sciences 15 36499306
2019 Identification of New HIV-1 Circulating Recombinant Forms CRF81_cpx and CRF99_BF1 in Central Western Brazil and of Unique BF1 Recombinant Forms. Frontiers in microbiology 15 30804902
2013 Transcriptional repression of AIB1 by FoxG1 leads to apoptosis in breast cancer cells. Molecular endocrinology (Baltimore, Md.) 15 23660594
2022 Zika virus induces FOXG1 nuclear displacement and downregulation in human neural progenitors. Stem cell reports 14 35714598
2019 In Silico Study of Rett Syndrome Treatment-Related Genes, MECP2, CDKL5, and FOXG1, by Evolutionary Classification and Disordered Region Assessment. International journal of molecular sciences 14 31717404
2015 FOXG1 expression shows correlation with neuronal differentiation in cerebellar development, aggressive phenotype in medulloblastomas, and survival in a xenograft model of medulloblastoma. Human pathology 14 26433703
2023 Role and mechanism of FOXG1-related epigenetic modifications in cisplatin-induced hair cell damage. Frontiers in molecular neuroscience 13 37181652
2023 Expanding genotype-phenotype correlations in FOXG1 syndrome: results from a patient registry. Orphanet journal of rare diseases 13 37308910
2022 Paving Therapeutic Avenues for FOXG1 Syndrome: Untangling Genotypes and Phenotypes from a Molecular Perspective. International journal of molecular sciences 13 35055139
2022 Behavioral Phenotypes of Foxg1 Heterozygous Mice. Frontiers in pharmacology 13 35754477
2019 Cognition and Evolution of Movement Disorders of FOXG1-Related Syndrome. Frontiers in neurology 13 31316448
2017 Nitric oxide promotes epidermal stem cell proliferation via FOXG1-c-Myc signalling. Nitric oxide : biology and chemistry 13 29248687

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