Affinage

FOXG1

Forkhead box protein G1 · UniProt P55316

Length
489 aa
Mass
52.4 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXG1 is a winged-helix transcription factor that serves as a master regulator of forebrain development, controlling neural progenitor proliferation, neuronal fate specification, cortical lamination, and post-mitotic neuronal survival and plasticity. In the nucleus, FOXG1 represses Cajal-Retzius cell fate, Wnt ligands, p21, Reelin, Robo1, and Slit3 through transcriptional repressor complexes with TLE1/Groucho and RP58, while its subcellular localization is antagonistically regulated by CKI-mediated Ser19 phosphorylation (nuclear import, maintaining progenitor state) and FGF/Akt-mediated Thr271 phosphorylation (nuclear export, promoting differentiation) (PMID:17435750, PMID:14704420, PMID:30392794, PMID:16314515). Beyond canonical transcriptional repression, FOXG1 acts posttranscriptionally by associating with the DROSHA/DDX5 microprocessor to regulate miR200 family biogenesis, and it promotes neuronal survival downstream of IGF-1/Akt signaling by counteracting MeCP2-e2-mediated apoptosis (PMID:30539330, PMID:21228151, PMID:22357867). FOXG1 additionally regulates autophagy in cochlear hair cells and astrocytes by binding the MAP1LC3B promoter, and its overexpression shifts neural progenitor output toward GABAergic inhibitory neurons at the expense of gliogenesis (PMID:34006186, PMID:38110963, PMID:26186191).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2004 High

    Establishing that FOXG1 is constitutively required to suppress the earliest-born cortical neuron fate (Cajal-Retzius cells) resolved why telencephalic progenitors do not default to CR identity and revealed FOXG1 as a fate-suppressing transcription factor rather than simply a growth factor.

    Evidence Foxg1 null and conditional knockout in mouse cortical progenitors with CR cell quantification

    PMID:14704420

    Open questions at the time
    • Downstream transcriptional targets mediating CR suppression not identified
    • Whether FOXG1 acts cell-autonomously in all CR progenitor subtypes unknown
  2. 2005 High

    Demonstrating that Foxg1 loss lengthens cell cycle prematurely, depletes progenitors through excess neurogenic divisions, and elevates BMP signaling established FOXG1 as a gatekeeper of progenitor pool size through cell cycle regulation and BMP pathway antagonism.

    Evidence BrdU/IdU double-labeling and phospho-Smad immunohistochemistry in Foxg1 null mice

    PMID:15893304

    Open questions at the time
    • Whether FOXG1 directly represses BMP pathway genes or acts indirectly not resolved
    • Mechanism linking FOXG1 to cell cycle lengthening not defined at the promoter level
  3. 2005 High

    Identifying TLE1/Groucho as a corepressor partner and Grg6 as a competitive inhibitor of the FOXG1-TLE1 complex provided the first molecular architecture for FOXG1-mediated transcriptional repression and a mechanism for tuning its activity.

    Evidence Yeast two-hybrid, co-immunoprecipitation, reporter assays, and RNAi in cortical progenitors

    PMID:16314515

    Open questions at the time
    • Genome-wide targets of the FOXG1-TLE1 complex in progenitors not mapped at this stage
    • Structural basis for Grg6 competition with TLE1 unknown
  4. 2007 High

    Revealing that CKI phosphorylation of Ser19 drives nuclear import while FGF/Akt phosphorylation of Thr226 drives nuclear export resolved how extracellular signals toggle FOXG1 between progenitor maintenance and differentiation.

    Evidence Phosphosite mutagenesis, kinase inhibitors, and subcellular localization imaging in Xenopus, mouse forebrain, and OP27 cells

    PMID:17435750

    Open questions at the time
    • Nuclear export receptor mediating Akt-dependent shuttling not identified
    • Whether additional phosphorylation sites cooperate in vivo unknown
  5. 2007 Medium

    Showing that Foxg1 haploinsufficiency reduces intermediate progenitor cells coincident with p21 upregulation established p21 as a key cell-cycle exit target repressed by FOXG1 in the subventricular zone.

    Evidence Foxg1 heterozygous mouse with BrdU, Tbr2, and p21 co-localization

    PMID:18065723

    Open questions at the time
    • Direct FOXG1 binding to the p21 promoter in neural progenitors not shown
    • Single lab observation awaiting independent replication
  6. 2009 High

    Epistasis experiments in zebrafish and mouse demonstrated that FOXG1 integrates Shh and Wnt signaling by acting as a Shh effector for ventral identity while directly repressing Wnt ligands to restrict dorsal signaling.

    Evidence Genetic epistasis across species combined with direct transcriptional repression assays

    PMID:19386266

    Open questions at the time
    • Specific Wnt ligand promoter elements bound by FOXG1 not mapped
    • Quantitative contribution of FOXG1-mediated Wnt repression versus other dorsoventral patterning genes unclear
  7. 2011 High

    Identifying that IGF-1/Akt phosphorylates Thr271 of FOXG1 to promote post-mitotic neuronal survival extended FOXG1 function beyond progenitor fate to a survival factor in differentiated neurons, linking it to the IGF-1/Akt pathway.

    Evidence Phosphomimetic mutations, Akt inhibition, IGF-1 treatment in cerebellar granule neurons

    PMID:21228151

    Open questions at the time
    • Survival-specific transcriptional targets of FOXG1 in neurons not identified
    • Whether Thr271 phosphorylation status differs from the Thr226 export signal in vivo needs clarification
  8. 2012 High

    Discovering that FOXG1 levels must oscillate during cortical migration — downregulation to set laminar identity (via Unc5D) and re-expression to exit the multipolar phase — revealed that dynamic FOXG1 dosage, not just presence/absence, orchestrates cortical plate assembly.

    Evidence Conditional Cre/lox strategies with in vivo migration imaging in mouse

    PMID:22726835

    Open questions at the time
    • Signals triggering the transient FOXG1 downregulation not defined
    • Whether the same oscillation applies to all cortical layers unknown
  9. 2012 High

    Showing that MeCP2-e2 directly interacts with FOXG1 and that FOXG1 antagonizes MeCP2-e2-mediated apoptosis via Akt provided a molecular link between FOXG1 and Rett syndrome-related pathways.

    Evidence Reciprocal co-immunoprecipitation, forced expression/knockdown, IGF-1/Akt epistasis in cerebellar granule neurons

    PMID:22357867

    Open questions at the time
    • Whether the FOXG1-MeCP2 interaction occurs on chromatin or in the nucleoplasm not resolved
    • Relevance to FOXG1-related encephalopathy versus Rett syndrome not tested in patient cells
  10. 2015 High

    Demonstrating that FOXG1 overexpression drives excess GABAergic neuron production in ASD patient-derived organoids connected FOXG1 dosage to autism-relevant excitatory/inhibitory imbalance in human tissue.

    Evidence FOXG1 knockdown in iPSC-derived 3D brain organoids with transcriptome analysis

    PMID:26186191

    Open questions at the time
    • Which FOXG1 target genes mediate the GABAergic fate shift not identified
    • Whether FOXG1 overexpression is cause or consequence of upstream ASD gene network changes not fully separated
  11. 2018 High

    ChIP-seq identification of direct FOXG1-RP58 complex targets (Robo1, Slit3, Reelin) in pyramidal neurons, and the finding that neuron-specific Foxg1 heterozygosity causes corpus callosum agenesis, defined the gene-regulatory circuit controlling callosal axon guidance downstream of FOXG1.

    Evidence ChIP-seq for FOXG1-RP58 binding, conditional heterozygous knockout, axon tracing in mouse

    PMID:30392794

    Open questions at the time
    • Whether the FOXG1-RP58 complex operates in other neuron types beyond cortical pyramidal neurons unknown
    • Structural basis of FOXG1-RP58 interaction not defined
  12. 2018 High

    Discovery that FOXG1 associates with the DROSHA/DDX5 microprocessor to regulate miR200 biogenesis established an unexpected posttranscriptional role for FOXG1 independent of its DNA-binding function, broadening its mechanistic repertoire.

    Evidence Co-immunoprecipitation of FOXG1/DDX5/DROSHA, genome-wide small RNA-seq, proteomics in Foxg1 cre/+ hippocampi

    PMID:30539330

    Open questions at the time
    • Whether FOXG1 DNA-binding domain is dispensable for microprocessor interaction not tested
    • Full repertoire of FOXG1-regulated miRNAs beyond miR200 family not characterized
  13. 2018 High

    Genome-wide ChIP-seq in glioblastoma-initiating cells confirmed that FOXG1 and TLE1 co-occupy target promoters including CHAC1 and negative regulators of Notch signaling, extending the FOXG1-TLE1 repressor paradigm to brain tumor stem cells.

    Evidence ChIP-seq and RNA-seq in patient-derived glioblastoma BTICs

    PMID:29316219

    Open questions at the time
    • Whether FOXG1-TLE1 targets in glioblastoma overlap substantially with those in normal progenitors not compared
    • Functional necessity of individual target genes for tumor maintenance not tested
  14. 2020 High

    Solving the crystal structure of the FOXG1 DNA-binding domain at 1.6 Å revealed a unique wing2 architecture among forkhead proteins and provided a structural framework for interpreting disease-causing mutations that disrupt DNA binding, thermal stability, or both.

    Evidence X-ray crystallography with mutagenesis of disease-causing variants

    PMID:33058871

    Open questions at the time
    • Full-length FOXG1 structure including disordered regions not solved
    • Structure of FOXG1 in complex with TLE1 or RP58 corepressors not available
  15. 2021 Medium

    Establishing that FOXG1 activates autophagy to protect cochlear hair cells from age-related and cisplatin-induced ROS accumulation expanded FOXG1 function to a cytoprotective autophagy regulator outside the brain, with direct binding to the MAP1LC3B promoter later confirmed.

    Evidence FOXG1 knockdown in OC-1 cells and aging cochlear explants; autophagy flux, ROS, and apoptosis assays; CUT&RUN at MAP1LC3B promoter

    PMID:34006186 PMID:38110963

    Open questions at the time
    • Whether FOXG1-mediated autophagy regulation operates in CNS neurons not tested
    • Direct transcriptional program downstream of FOXG1 in hair cells beyond MAP1LC3B not mapped genome-wide

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length FOXG1 structure, the genome-wide overlap of FOXG1 targets across cell types, whether the microprocessor role requires DNA-binding-independent domains, and the precise mechanism by which FOXG1 dosage oscillations are controlled during cortical migration.
  • Full-length structural model unavailable
  • Systematic comparison of FOXG1 chromatin occupancy across developmental stages and cell types lacking
  • Signals controlling dynamic FOXG1 downregulation during multipolar phase not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-9612973 Autophagy 3 R-HSA-8953854 Metabolism of RNA 1
Partners
ARBMI1DDX5DROSHAGRG6MECP2RP58TLE1
Complex memberships
DROSHA/DDX5 microprocessorFOXG1-RP58 repressor complexFOXG1-TLE1 repressor complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 FOXG1 overexpression is responsible for the overproduction of GABAergic inhibitory neurons in ASD-derived brain organoids, demonstrating a direct role in shifting neuron fate toward GABAergic lineage during development. RNA interference knockdown in iPSC-derived 3D neural organoids with transcriptome and gene network analysis Cell High 26186191
2004 Foxg1 actively suppresses Cajal-Retzius cell fate in cortical progenitors; in Foxg1 null mutants an excess of Cajal-Retzius neurons is produced, and conditional inactivation at later stages demonstrates Foxg1 is constitutively required to suppress this earliest-born neuron fate. Foxg1 null mutation and conditional genetic inactivation in mouse cortical progenitors Science High 14704420
2005 Foxg1 is required for induction of ventral telencephalic cell fate; its loss results in premature cell cycle lengthening, reduced apoptosis in the rostral domain, coinciding with reduced Fgf8 expression; and from E11.5 onward, excess neurogenic divisions deplete the progenitor pool, with increased BMP signaling (phospho-Smad1/5/8) accompanying premature differentiation. Foxg1 null mouse mutant analysis with BrdU/IdU double labeling for cell cycle kinetics, immunohistochemistry for phospho-Smad1/5/8 Developmental biology High 15893304
2007 FoxG1 nuclear-cytoplasmic localization is regulated post-translationally: CKI phosphorylation of Ser19 promotes nuclear import (maintaining progenitor state), while FGF-induced phosphorylation of Thr226 via Akt kinase promotes nuclear export (promoting neuronal differentiation). These two signals antagonistically regulate FoxG1 activity. Phosphorylation site mutagenesis, pharmacological inhibition of CKI and Akt, subcellular localization imaging in Xenopus, mouse forebrain, and OP27 cell line Nature cell biology High 17435750
2009 Foxg1 coordinates two opposing telencephalic signaling centers: it acts as a key downstream effector of Shh signaling to induce subpallial (ventral) identity, and it directly transcriptionally represses Wnt ligands to restrict dorsal Wnt signaling center activity to the roof plate. Genetic epistasis in zebrafish and mouse, direct transcriptional repression assays Developmental cell High 19386266
2012 Dynamic regulation of FoxG1 expression in the intermediate zone is essential for cortical plate assembly: downregulation of FoxG1 at the onset of the multipolar cell phase induces Unc5D expression (setting laminar identity), while re-expression of FoxG1 is required for cells to exit the multipolar phase and enter the cortical plate. Conditional genetic strategies (Cre/lox) in mouse with in vivo imaging of neuron migration Neuron High 22726835
2008 MicroRNA-9 targets the 3' UTR of Foxg1 mRNA to negatively regulate Foxg1 protein levels, thereby modulating Cajal-Retzius cell differentiation in the medial pallium; miR-9 overexpression causes ectopic Reelin-positive cells, while miR-9 inhibition reduces cortical hem and CR cell populations. Gain- and loss-of-function of miR-9 by electroporation in developing mouse telencephalon, 3'UTR reporter assays The Journal of neuroscience High 18842901
2005 BF-1/FoxG1 represses transcription together with the corepressor Gro/TLE1, while the related protein Grg6 interacts with BF-1 and suppresses BF-1-mediated transcriptional repression by interfering with TLE1 binding; coexpression of Grg6 and BF-1 decreases progenitor proliferation and increases neuronal differentiation. Yeast two-hybrid, co-immunoprecipitation, transcriptional reporter assays, RNAi knockdown in cortical progenitors Molecular and cellular biology High 16314515
2011 FoxG1 promotes survival of postmitotic neurons via an Akt-dependent mechanism: IGF-1 activates Akt which phosphorylates Thr271 of FoxG1 to promote neuronal survival; the N-terminal 36 residues and DNA-binding (Asp219) are required; FoxG1 acts downstream of IGF-1/Akt signaling and is required to maintain neuronal survival. Ectopic expression, dominant-negative FoxG1, phosphomimetic mutations, Akt pharmacological inhibition, IGF-1 treatment in cerebellar granule neurons The Journal of neuroscience High 21228151
2012 MeCP2-e2 isoform interacts directly with FoxG1 and promotes neuronal apoptosis; elevated FoxG1 expression inhibits MeCP2-e2 neurotoxicity, an effect dependent on Akt-mediated phosphorylation of FoxG1; reduced FoxG1 expression releases MeCP2-e2 to promote neuronal death. Co-immunoprecipitation of MeCP2-e2 and FoxG1, forced expression and knockdown in cerebellar granule neurons, IGF-1/Akt pharmacological manipulation The Journal of neuroscience High 22357867
2012 The chromatin remodeler Snf2l binds the Foxg1 locus and represses Foxg1 expression at midneurogenesis; Snf2l mutant mice show increased Foxg1 expression, forebrain hypercellularity, and increased progenitor expansion, all rescued by reducing Foxg1 dosage. ChIP at Foxg1 locus, Snf2l/Foxg1 double mutant genetic rescue experiment in mouse Developmental cell High 22516202
2015 AKT3(E17K) mutation in FMCD activates PI3K-AKT-mTOR signaling, which derepresses reelin transcription in a FOXG1-dependent manner, causing non-cell-autonomous neuronal migration defects; blocking AKT signaling or inactivating reelin restores migration, placing FOXG1 as an intermediary repressor of reelin downstream of AKT. In utero electroporation of FMCD mutation in mouse brain, treatment with AKT inhibitors and anti-reelin, analysis of FOXG1-dependent reelin transcription Nature medicine High 26523971
2018 FOXG1 forms a transcriptional complex with RP58 in pyramidal neurons; the FOXG1-RP58 complex directly binds and represses Robo1, Slit3, and Reelin genes to establish callosal axon guidance and proper neuronal migration; neuron-specific loss of one Foxg1 allele causes cortical hypoplasia and corpus callosum agenesis. ChIP-seq for FOXG1-RP58 complex binding; conditional and heterozygous Foxg1 knockout in cortical neurons; axon tracing Neuron High 30392794
2009 Foxg1 restricts sensory fate in the inner ear and is required for proper separation between anterior and lateral cristae; in Foxg1-null mice, the prospective lateral crista is present but lost, and the lateral canal forms without a lateral ampulla. Foxg1 null mouse mutant analysis with gene expression and genetic fate-mapping Developmental dynamics Medium 19842177
2007 Foxg1 represses generation of both cortical hem-derived and PSB-derived Cajal-Retzius populations; loss of Foxg1 at E13 expands PSB-phenotype CR cells without expanding BMP/Wnt dorsomedial signaling, indicating Foxg1 acts downstream or independently of these signals to suppress CR fate. Conditional Foxg1 inactivation at E13, Gli3 double mutant analysis in mouse The Journal of neuroscience High 17928452
2007 Foxg1 haploinsufficiency reduces the intermediate progenitor cell (IPC) population in the subventricular zone, coinciding with increased expression of the cell-cycle inhibitor p21 in VZ and SZ; Foxg1 is required to suppress p21-dependent cell-cycle exit and enable IPC expansion. Foxg1 heterozygous mouse analysis with BrdU labeling, Tbr2 and Brn2 immunostaining, p21 colocalization Cerebral cortex Medium 18065723
2010 Foxg1 overexpression inhibits gliogenesis and promotes neuronogenesis through distinct mechanisms in cortical progenitors; Foxg1 also dramatically stimulates neurite outgrowth. Lentiviral overexpression in embryonic cortical progenitors with multiplex cytofluorometry and immunocytofluorescence using cell-type-specific reporters Stem cells Medium 20506244
2009 FOXG1 promotes survival of aging cochlear hair cells by regulating autophagy; siRNA knockdown of Foxg1 in hair cell-like OC-1 cells increases cell death and apoptosis after LPS injury, while FoxG1 expression and autophagy levels change coordinately under inflammatory and aging conditions. siRNA knockdown in OC-1 cells and cochlear explants, LPS and D-galactose aging models, autophagy and apoptosis assays Redox biology Medium 31731101
2021 FOXG1 promotes hair cell survival in presbycusis through activation of the autophagy pathway; FOXG1 inhibition decreases autophagy activity, leading to ROS accumulation and apoptosis; aspirin increases FOXG1 expression, activates autophagy, reduces ROS, and promotes HC survival. FOXG1 knockdown in OC-1 cells and aging cochlear explants; rapamycin and bafilomycin treatment to modulate autophagy; ROS and apoptosis assays Autophagy Medium 34006186
2013 FoxG1 interacts with Bmi1 in medulloblastoma brain tumor-initiating cells (BTICs) to regulate self-renewal and tumor initiation; reciprocal promoter occupancy between FoxG1 and Bmi1 was identified in CD15+ MB stem cells. ChIP for reciprocal promoter occupancy, sphere-forming and tumor initiation assays in mice Stem cells Medium 23592496
2018 FOXG1 and TLE1 form a transcriptional repressor complex in glioblastoma-initiating cells; ChIP-Seq identified 150 direct FOXG1 targets, several shared with TLE1, including CHAC1 and other negative regulators of NOTCH signaling. ChIP-Seq and RNA-Seq in patient-derived glioblastoma BTICs Molecular oncology High 29316219
2007 FoxG1 functions as a corepressor of the androgen receptor (AR); the C-terminal region (aa 175-489) of FoxG1 interacts with AR (aa 325-919) in yeast two-hybrid and pull-down assays, and full-length FoxG1 strongly represses AR-mediated transactivation. Yeast two-hybrid, pull-down assays, one- and two-hybrid functional assays The Journal of steroid biochemistry and molecular biology Medium 17482455
2009 FOXG1 contributes to TGF-β resistance in ovarian cancer by selectively blocking TGF-β-induced p21WAF1/CIP1 expression; FOXG1 inhibits p21 promoter activity in a p53-independent manner, and its knockdown reduces cell proliferation and increases p21 expression. Stable overexpression and shRNA knockdown of FOXG1, luciferase reporter assay for p21 promoter, XTT proliferation assay British journal of cancer Medium 19755996
2011 GFP-FoxG1 associates with chromatin in two kinetic populations: a reversibly bound fraction and a smaller irreversibly bound fraction; disease-causing mutations alter these chromatin binding kinetics, with different mutations showing distinct patterns of chromatin affinity. FRAP (fluorescence recovery after photobleaching) of GFP-FoxG1 fusion proteins including disease-causing mutants in cells Clinical genetics Medium 22091895
2020 Crystal structure of FOXG1 DNA-binding domain (DBD) in complex with the forkhead consensus DNA site DBE2 at 1.6 Å resolution reveals a winged-helix fold with a unique wing2 architecture containing two β-strands distinct from all other FOX-DBD wing2 folds; disease-causing mutations within DBD affect DNA binding, protein thermal stability, or both. X-ray crystallography at 1.6 Å, mutation assays for DNA binding and thermal stability Journal of molecular biology High 33058871
2018 FOXG1 regulates miR200b/a/429 biogenesis by associating with the microprocessor complex through interaction with DDX5/p68; FOXG1 and DDX5 associate with DROSHA, and this posttranscriptional mechanism controls PRKAR2B expression in the hippocampus. Genome-wide small RNA sequencing, quantitative proteomics, co-immunoprecipitation of FOXG1/DDX5/DROSHA, RNA-Seq of Foxg1 cre/+ hippocampi Molecular neurobiology High 30539330
2017 Conditional disruption of Foxg1 in the subpallium (using Dlx5/6-Cre) impairs interneuron development by strongly downregulating migration receptors (Robo1, EphA4, CXCR4/7) and upregulating Dlx1/2, Mash1, and Prox1, resulting in migration defects and shorter neurites. Conditional knockout using Dlx5/6-Cre × Foxg1fl/fl mice, in vitro migration assay, immunostaining and qPCR Cerebral cortex Medium 26620267
2018 FOXG1 hierarchically regulates Lhx2 expression in the cortical primordium; in the absence of Foxg1, residual Lhx2 suppresses cortical hem fate, and Foxg1 restricts the temporal window during which loss of Lhx2 causes cortical-to-hem transformation. Foxg1/Lhx2 single and double conditional knockouts in mouse, in situ hybridization and immunostaining Development High 29229772
2019 Conditional knockdown of Foxg1 in cochlear Sox2+ supporting cells and Lgr5+ progenitors promotes trans-differentiation of supporting cells into hair cells (especially inner hair cells) without cell division, likely through inhibition of Notch signaling; cell cycle and Notch pathway genes are significantly downregulated in Foxg1 cKD cochlear SCs. Sox2-CreER/Lgr5-CreER × Foxg1loxp/loxp conditional knockdown, EdU assay, lineage tracing, sphere-forming assay, qPCR Cellular and molecular life sciences High 31485717
2019 Conditional disruption of Foxg1 in mature neurons (using Camk2a-CreER) impairs spatial learning, fear memory, and long-term potentiation, and reduces dendritic arborization and spine densities in hippocampal pyramidal neurons, demonstrating a role for FOXG1 in maintaining neural plasticity in adult neurons. Tamoxifen-induced conditional KO in adult neurons, Morris water maze, fear conditioning, LTP electrophysiology, dendritic morphology analysis Molecular brain High 31253171
2013 FoxG1 directly represses AIB1 gene transcription by being recruited to the AIB1 promoter region, where it displaces the activating complex (AIB1, E2F1, Sp1, p300), thereby reducing AIB1 expression and promoting apoptosis in breast cancer cells. ChIP showing FoxG1 recruitment to AIB1 promoter, overexpression experiments, rescue with AIB1 re-expression in MCF-7 cells Molecular endocrinology Medium 23660594
2019 Foxg1 stimulates dendrite elongation in neocortical pyramidal neurons by upregulating Hes1, which in turn upregulates pCreb1 (via PKA and AKT, with reduced PP1/PP2A activity) and downregulates Syt and Ndr1 (antagonizers of dendrite elongation). Foxg1 overexpression in vivo and in vitro, pharmacological inhibition of PKA and AKT, Hes1 and pCreb1 expression analysis Cerebral cortex Medium 29385539
2019 High Foxg1 expression in neocortical stem cells antagonizes astrogenesis by downregulating key effectors channeling neural stem cells toward astroglial fates and by preventing activation of astroglial differentiation programs; Foxg1 levels specifically decline during the neuronogenic-to-gliogenic transition. Lentiviral overexpression in mouse and human neocortical precursors, cytofluorometry with cell-type-specific reporters Cerebral cortex Medium 30821834
2022 ZIKV infection causes nuclear displacement and downregulation of FOXG1 in human neural progenitors; EGF and FGF2 contribute to nuclear re-localization, and the Thr271 residue in the AKT domain is required for apoptosis protection; the C-terminus (residues 428-481) is a critical domain for FOXG1 function. ZIKV infection of human neural progenitors, progressive deletion mapping of FOXG1 domains, AKT inhibition, growth factor treatment Stem cell reports Medium 35714598
2023 CB2R activation on astrocytes inhibits FOXG1 binding to the MAP1LC3B autophagy gene promoter (identified by CUT&RUN), increases autophagy, facilitates NLRP3 degradation via the autophagy-lysosome pathway, and reduces neuroinflammation in a Parkinson's disease model. CUT&RUN to identify FOXG1 binding to MAP1LC3B; CB2R agonist/antagonist treatment; foxg1 adenovirus knockdown in mice; autophagy flux assays Journal of neuroinflammation Medium 38110963
2020 Conditional deletion of Foxg1 in oligodendrocyte precursor cells (OPCs) alleviates demyelination and accelerates remyelination via the Wnt/GSK-3β/β-catenin signaling pathway; Foxg1 knockout decreases OPC proliferation and accelerates differentiation into mature oligodendrocytes, an effect abolished by GSK-3β inhibitor SB216763. Foxg1 conditional knockout in cuprizone mouse model, OPC proliferation/differentiation assays, SB216763 (GSK-3β inhibitor) treatment in vitro Neuroscience bulletin Medium 33015737
2023 FOXG1 promotes epigenetic regulation of autophagy in cochlear hair cells under cisplatin ototoxicity: cisplatin increases H3K9me2 (via G9a) at FOXG1-regulated loci, reducing FOXG1 expression, miRNA expression, and autophagy, leading to ROS accumulation and apoptosis; BIX01294 (G9a inhibitor) or FOXG1 overexpression rescues hair cells. Cisplatin CBA/CaJ mouse model, G9a inhibitor BIX01294, FOXG1 overexpression, miRNA and autophagy assays Frontiers in molecular neuroscience Medium 37181652

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 823 26186191
2005 Foxg1 is required for specification of ventral telencephalon and region-specific regulation of dorsal telencephalic precursor proliferation and apoptosis. Developmental biology 327 15893304
2004 Foxg1 suppresses early cortical cell fate. Science (New York, N.Y.) 311 14704420
2000 Transcriptional repression by blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase. Molecular and cellular biology 273 10713181
1994 Expression of winged helix genes, BF-1 and BF-2, define adjacent domains within the developing forebrain and retina. Journal of neurobiology 181 7815060
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 163 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
2019 The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways. Redox biology 151 31731101
2011 Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains. Molecular cell 149 22099305
2012 Dynamic FoxG1 expression coordinates the integration of multipolar pyramidal neuron precursors into the cortical plate. Neuron 126 22726835
2021 FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway. Autophagy 117 34006186
2009 Integration of telencephalic Wnt and hedgehog signaling center activities by Foxg1. Developmental cell 110 19386266
2007 The role of Foxg1 and dorsal midline signaling in the generation of Cajal-Retzius subtypes. The Journal of neuroscience : the official journal of the Society for Neuroscience 105 17928452
2019 Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea. Cellular and molecular life sciences : CMLS 100 31485717
2015 An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development. Nature medicine 97 26523971
2015 VEGF-Mediated Induction of PRD1-BF1/Blimp1 Expression Sensitizes Tumor Vasculature to Oncolytic Virus Infection. Cancer cell 95 26212250
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
2007 Foxg1 haploinsufficiency reduces the population of cortical intermediate progenitor cells: effect of increased p21 expression. Cerebral cortex (New York, N.Y. : 1991) 83 18065723
2007 The neural progenitor-specifying activity of FoxG1 is antagonistically regulated by CKI and FGF. Nature cell biology 81 17435750
2017 FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants. Genetics in medicine : official journal of the American College of Medical Genetics 78 28661489
2011 FoxG1 promotes the survival of postmitotic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 76 21228151
2018 FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical Connections. Neuron 73 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
2012 Isoform-specific toxicity of Mecp2 in postmitotic neurons: suppression of neurotoxicity by FoxG1. The Journal of neuroscience : the official journal of the Society for Neuroscience 67 22357867
2020 Transcription and Beyond: Delineating FOXG1 Function in Cortical Development and Disorders. Frontiers in cellular neuroscience 64 32158381
2017 Evolutionary conservation and conversion of Foxg1 function in brain development. Development, growth & differentiation 58 28581027
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
2014 Epilepsy and outcome in FOXG1-related disorders. Epilepsia 53 24836831
2012 Snf2l regulates Foxg1-dependent progenitor cell expansion in the developing brain. Developmental cell 52 22516202
2009 Foxg1 is required for proper separation and formation of sensory cristae during inner ear development. Developmental dynamics : an official publication of the American Association of Anatomists 50 19842177
2019 FOXG1 Dose in Brain Development. Frontiers in pediatrics 49 31824897
2013 FoxG1 interacts with Bmi1 to regulate self-renewal and tumorigenicity of medulloblastoma stem cells. Stem cells (Dayton, Ohio) 49 23592496
2012 14q12 and severe Rett-like phenotypes: new clinical insights and physical mapping of FOXG1-regulatory elements. European journal of human genetics : EJHG 44 22739344
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 43 37852337
2009 Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of p21WAF1/CIP1 expression in ovarian cancer. British journal of cancer 43 19755996
2013 Anti-inflammatory compounds of "Qin-Jiao", the roots of Gentiana dahurica (Gentianaceae). Journal of ethnopharmacology 40 23506994
2005 Antagonistic effects of Grg6 and Groucho/TLE on the transcription repression activity of brain factor 1/FoxG1 and cortical neuron differentiation. Molecular and cellular biology 39 16314515
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2013 Quantitative detection of viable Bifidobacterium bifidum BF-1 cells in human feces by using propidium monoazide and strain-specific primers. Applied and environmental microbiology 37 23354719
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1992 Regulation of human immunodeficiency virus enhancer function by PRDII-BF1 and c-rel gene products. Journal of virology 36 1727488
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2023 Targeting CB2R in astrocytes for Parkinson's disease therapy: unraveling the Foxg1-mediated neuroprotective mechanism through autophagy-mediated NLRP3 degradation. Journal of neuroinflammation 25 38110963
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