| 2000 |
Targeted deletion of HFH-4 (FOXJ1) in mice results in complete absence of motile 9+2 cilia in airway epithelial cells, while sensory 9+0 cilia (e.g., olfactory) remain intact; ultrastructural analysis revealed the defect is due to abnormal centriole migration and/or failure of apical membrane docking of basal bodies, demonstrating FOXJ1 is required for basal body positioning/anchoring specifically in cells producing motile cilia. |
Gene targeting (knockout mice), transmission electron microscopy, in situ hybridization, immunohistochemistry |
American journal of respiratory cell and molecular biology |
High |
10873152
|
| 1999 |
HFH-4 (FOXJ1) protein is specifically localized to ciliated epithelial cells (lung, trachea, nose, choroid plexus, ependyma, oviduct) and in spermatids coincident with flagella generation, and its expression temporally precedes cilia appearance during development, consistent with a role in directing the ciliated cell differentiation program. |
Immunohistochemistry with anti-HFH-4 antibody, in situ hybridization, temporal expression analysis in developing mouse lung |
American journal of respiratory cell and molecular biology |
Medium |
10423398
|
| 1997 |
Recombinant HFH-4 protein binds the DNA consensus sequence HWDTGTTTGTTTA (determined by in vitro selection), and functions as a transcriptional activator in cotransfection assays; it forms specific protein-DNA complexes with promoters of prothrombin, beta-amyloid precursor protein, CFTR, alpha2-macroglobulin, growth hormone receptor, IGF-II, HNF-3alpha, and CCSP genes, identifying these as candidate target genes. |
In vitro DNA-binding site selection (SELEX) with recombinant protein, EMSA, cotransfection transcriptional activation assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
9096351
|
| 2003 |
In primary culture, Foxj1-null airway epithelial cells contain cilia precursor basal bodies but these fail to dock with the apical membrane; reconstitution of Foxj1 in null cells restores basal body organization and apical docking, leading to axoneme growth. Delivery of Foxj1 to wild-type or non-airway cells did not enhance ciliogenesis, indicating Foxj1 functions specifically in late-stage ciliogenesis (basal body docking and axoneme formation) in cells already committed to the ciliated phenotype. |
Primary cell culture of Foxj1-null mouse airway epithelial cells, viral delivery of Foxj1 to null and wild-type cells, ultrastructural analysis |
American journal of physiology. Lung cellular and molecular physiology |
High |
12818891
|
| 2004 |
Microarray analysis of foxj1+/+ vs. foxj1-/- mouse pulmonary epithelium identified calpastatin (a calpain inhibitor) as a Foxj1-dependent gene; in null cells, reduced calpastatin leads to elevated calpain activity, which degrades ezrin. Loss of ezrin and EBP-50 prevents basal body anchoring to the apical cytoskeleton. Treatment of foxj1-/- tracheal explants with a calpain inhibitor partially restored cilia, basal body apical localization, and ezrin/EBP-50 relocalization, establishing a Foxj1 → calpastatin → calpain → ezrin → basal body anchoring mechanism. |
Microarray, RNase protection assay, immunohistochemistry, western blot, immunoelectron microscopy, pharmacological calpain inhibitor rescue in tracheal explants |
Journal of cell science |
High |
14996907
|
| 2003 |
Foxj1 expression is required for apical localization of ezrin (but not moesin) in airway epithelial cells; Foxj1-null cells lack membrane-associated and threonine-phosphorylated apical ezrin, and downstream ezrin-associated proteins EBP-50 and the beta2 adrenergic receptor also fail to localize apically, demonstrating Foxj1 differentially regulates ERM proteins to organize multi-protein complexes at the apical membrane. |
Analysis of Foxj1-null mouse airway epithelial cells, immunofluorescence, western blot, comparison of differentiated vs. undifferentiated cells |
Journal of cell science |
High |
14625387
|
| 2004 |
Foxj1 suppresses NF-κB transcriptional activity in vitro; Foxj1-deficient T cells exhibit increased NF-κB activity in vivo; Foxj1 regulates IκB proteins, particularly IκBβ, providing a mechanism by which Foxj1 modulates T cell activation and prevents autoimmunity. |
In vitro NF-κB reporter assays, analysis of Foxj1-knockout mice (multi-organ inflammation phenotype), NF-κB activity measurement in primary T cells |
Science (New York, N.Y.) |
High |
14963332
|
| 2007 |
Foxj1 expression coincides with and promotes formation of an apical web-like actin structure required for basal body docking during ciliogenesis; Foxj1-null mouse airway epithelial cells fail to dock basal bodies and lack apical actin. Foxj1 activated RhoA and RhoB, and Foxj1 expression persisted despite RhoA inhibition, placing Foxj1 upstream of RhoA in promoting cytoskeletal remodeling. Apical ezrin localization was also dependent on Foxj1, actin remodeling, and RhoA. |
Primary culture of Foxj1-null mouse airway cells, actin inhibitors, RhoA activation assays, immunofluorescence, basal body docking analysis |
Journal of cell science |
High |
17488776
|
| 2007 |
IL-13 treatment of human airway epithelium decreases foxj1 expression, mislocates basal bodies, and causes loss of apical ezrin, followed by loss of ciliated cells. A STAT-binding element was identified in the foxj1 promoter, and STAT-6 was shown to inhibit foxj1 expression, establishing an IL-13/STAT-6 → foxj1 suppression → cilia loss regulatory axis. |
Human airway epithelial cell culture, IL-13 treatment, foxj1 promoter analysis, STAT-6 cotransfection/inhibition assays, immunofluorescence |
American journal of respiratory cell and molecular biology |
Medium |
17541011
|
| 2008 |
Zebrafish foxj1a is a target of Hedgehog signaling in the floor plate; loss of foxj1a disrupts motile cilia assembly in floor plate cells, Kupffer's vesicle, and pronephric ducts; ectopic expression of foxj1a is sufficient to induce ectopic cilia resembling motile cilia; microarray analysis showed foxj1a activates a constellation of genes essential for motile cilia formation—establishing Foxj1 as a master transcriptional regulator of the motile ciliogenic program. |
Zebrafish morpholino knockdown, ectopic overexpression, microarray analysis of foxj1a-regulated transcriptome, scanning electron microscopy |
Nature genetics |
High |
19011630
|
| 2008 |
Xenopus and zebrafish Foxj1 is required for formation of cilia underlying left-right patterning (GRP/Kupffer's vesicle); Foxj1 morphants have severely shortened or absent cilia at these structures; misexpression of Foxj1 is sufficient to induce ectopic GRP-like cilia; microarray analysis shows Foxj1 induces motile cilia gene expression, establishing that Foxj1 specifies the node-like cilia subtype used in LR patterning. |
Xenopus and zebrafish morpholino knockdown, ectopic overexpression in frog embryos, microarray analysis, cilia imaging |
Nature genetics |
High |
19011629
|
| 2008 |
PITX2 binds the FoxJ1 promoter (chromatin immunoprecipitation) and activates it; Lef-1 and β-catenin interact with PITX2 to synergistically regulate the FoxJ1 promoter; FoxJ1 physically interacts with the PITX2 homeodomain and synergistically activates the FoxJ1 promoter (positive feedback); the ARS-associated PITX2 T68P mutant physically interacts with FoxJ1 but cannot activate the FoxJ1 promoter. |
Chromatin immunoprecipitation, cotransfection promoter-reporter assays, protein-protein interaction (co-immunoprecipitation), transgenic mouse fibroblasts |
Human molecular genetics |
High |
18723525
|
| 2010 |
Foxj1 expression in floor plate cells increases cilia length beyond that of primary cilia elsewhere; forced Foxj1 expression in neuroepithelial cells is sufficient to increase cilia length; Foxj1 expression in Shh-responsive cells attenuates Gli transcriptional activity (intracellular Shh signaling) in a cilia-dependent manner, establishing Foxj1 as a modulator of Shh signal transduction via its role in ciliogenesis. |
Chick and mouse Foxj1 overexpression, Foxj1 knockout mouse analysis, Gli reporter assays in Shh-responsive cell lines, cilia length measurements |
Development (Cambridge, England) |
High |
21098568
|
| 2011 |
Wnt/β-catenin signaling directly activates foxj1a transcription in zebrafish Kupffer's vesicle (KV) via Lef1/Tcf binding sites in the foxj1a enhancer; reduction of Wnt signaling causes shorter/fewer cilia, loss of motility, and LR patterning defects that are rescued by KV-targeted foxj1a overexpression; epistasis places Wnt signaling upstream of foxj1a expression and ciliogenesis. |
Zebrafish Wnt pathway manipulation (genetic and pharmacological), morpholino knockdown, foxj1a overexpression rescue, enhancer analysis with Lef1/Tcf site mutations, epistasis |
Development (Cambridge, England) |
High |
22190638
|
| 2012 |
In zebrafish and flatworm (Schmidtea mediterranea), FoxJ1 homologs from diverse phyletic groups can activate motile ciliary gene expression; inactivation of foxJ1 in S. mediterranea profoundly disrupts motile cilia differentiation, demonstrating evolutionary conservation of the FoxJ1-regulated motile ciliogenic program back to the origin of metazoans. |
Mis-expression assay in zebrafish embryos, RNAi knockdown in planaria, evolutionary genomic survey, cilia phenotype analysis |
PLoS genetics |
High |
23144623
|
| 2012 |
Foxj1 expressed from the Noto locus in mouse restores structurally normal motile cilia in Noto-null embryos, demonstrating Foxj1 is functionally sufficient for ciliogenesis in the node. However, Foxj1 alone cannot restore correct posterior positioning of cilia on node cells, showing Noto has a Foxj1-independent role in cilia positioning. Foxj1 acts upstream of Rfx3 in node ciliogenesis. |
Knock-in mouse (Foxj1 coding sequence replacing Noto), Foxj1 knockout mice, electron microscopy, nodal flow analysis, genetic epistasis |
Development (Cambridge, England) |
High |
22357932
|
| 2012 |
ATP4a is required for Wnt/β-catenin-regulated Foxj1 induction in the superficial mesoderm of Xenopus; ATP4 knockdown or pharmacological inhibition downregulates foxj1 expression and causes fewer, shortened, misaligned cilia in the GRP, establishing an ATP4a → Wnt/β-catenin → Foxj1 → cilia motility axis in LR axis determination. |
Xenopus morpholino knockdown, pharmacological inhibition, gene expression analysis, cilia phenotype quantification, epistasis |
Cell reports |
Medium |
22832275
|
| 2013 |
Transfection of FOXJ1 into resting human airway basal cells activates cilia-gene promoters and induces expression of ciliated cell genes; RFX3 alone cannot induce cilia-related gene expression but enhances FOXJ1-driven gene expression; co-immunoprecipitation demonstrated a direct physical interaction between FOXJ1 and RFX3, identifying RFX3 as a transcriptional co-activator of FOXJ1 in human ciliated cell differentiation. |
Human primary airway basal cell transfection, promoter-reporter assays, TaqMan PCR, co-immunoprecipitation (FOXJ1-RFX3 interaction), air-liquid interface differentiation |
Respiratory research |
High |
23822649
|
| 2016 |
p73 directly binds and regulates the Foxj1 locus (ChIP-seq in murine tracheal cells), and p73 knockout mice lose multiciliated cell differentiation; many phenotypes of p73 knockout (hydrocephalus, hippocampal dysgenesis, sterility, lung/ear/sinus inflammation) are explained by loss of ciliary biogenesis, placing p73 upstream of Foxj1 in the multiciliogenesis transcriptional hierarchy. |
p73/p63 ChIP-seq in murine tracheal cells, p73 knockout mouse analysis, histological and functional cilia analysis |
Cell reports |
High |
26947080
|
| 2019 |
Heterozygous de novo mutations in FOXJ1 cause a motile ciliopathy in humans; mutant respiratory epithelial cells generate fewer cilia per cell with mislocalized basal bodies; PTK2 (focal adhesion kinase) displays aberrant cytoplasmic localization in mutant cells, suggesting FOXJ1 controls basal body anchoring in part via PTK2 localization. |
Whole-exome/genome sequencing, high-speed video microscopy, transmission electron microscopy, immunofluorescence in patient-derived cells |
American journal of human genetics |
High |
31630787
|
| 2021 |
The m6A demethylase FTO demethylates FOXJ1 mRNA and thereby stabilizes it; depletion of Fto in Xenopus causes motile cilia defects and reduces Foxj1 mRNA levels; FTO depletion in primary human airway epithelium destabilizes FOXJ1 mRNA, leading to loss of ciliated cells and increase in goblet cells, establishing a conserved FTO → FOXJ1 mRNA stability → motile ciliogenesis axis. |
Xenopus Fto depletion, m6A sequencing/profiling, mRNA stability assays, human airway epithelial culture, Fto knockout mice, allergen challenge model |
Developmental cell |
High |
33761320
|
| 2016 |
Genome-wide expression profiling of Foxj1+/+ vs. Foxj1-/- mouse fetal lung and ventral node identified 326 candidate FOXJ1-dependent ciliogenesis genes, including 123 not previously linked to ciliogenesis; 59 of these are also NOTO/FOXJ1-dependent in the node, revealing distinct but overlapping downstream transcriptional programs for motile cilia in lung vs. node. |
Microarray hybridization of microdissected mouse airway epithelia (E14.5 vs E18.5; Foxj1+ vs Foxj1-/-), parallel Noto-null vs Noto+ profiling |
Developmental biology |
Medium |
27914912
|
| 2005 |
Foxj1 deficiency in B cells results in spontaneous and accentuated germinal center formation, pathogenic autoantibodies, and exaggerated humoral responses, correlated with excessive NF-κB and IL-6 activity; Foxj1 is required to regulate IκBβ in B cells, extending the NF-κB suppression mechanism to the B cell compartment. |
B cell-specific analysis of Foxj1 knockout mice, germinal center staining, autoantibody measurement, NF-κB activity and IκBβ protein analysis |
Journal of immunology (Baltimore, Md. : 1950) |
Medium |
16002694
|
| 2005 |
Ectopic expression of Foxj1 (CD2-Foxj1 transgene) in T cells causes peripheral T cell lymphopenia associated with accumulation of mature single-positive thymocytes; transgenic thymocytes show impaired exodus in response to CCL19 apparently independent of CCR7, S1P1, and NF-κB, identifying a novel role for Foxj1 in regulating thymic egress. |
CD2-Foxj1 transgenic mice on MRL/lpr background, lymphocyte phenotyping, adoptive transfer studies, CCL19 migration assays |
Journal of immunology (Baltimore, Md. : 1950) |
Medium |
16339515
|
| 2016 |
CFAP157 protein localizes to basal bodies and interacts with tubulin and centrosomal protein CEP350; Cfap157 is expressed in motile ciliated tissues in a FOXJ1-dependent manner; Cfap157 knockout mice are infertile in males, with sperm showing impaired motility and aberrant axonemal loops, supernumerary axonemal profiles, and defective flagellar ultrastructure, establishing CFAP157 as a sperm-specific FOXJ1 effector. |
FOXJ1-dependent expression analysis (zebrafish/mouse), Cfap157 knockout mice, protein localization (basal bodies), co-immunoprecipitation with tubulin/CEP350, electron microscopy of sperm |
Development (Cambridge, England) |
High |
27965440
|
| 2020 |
Cfap206 is a FOXJ1 target gene expressed in motile ciliated tissues; CFAP206 protein localizes to basal bodies and axonemes; Cfap206 knockout mice display male infertility, hydrocephalus, and impaired mucociliary clearance; electron tomography of knockout sperm flagella indicates a role in radial spoke formation, analogous to FAP206 in Tetrahymena. |
Foxj1-dependence analysis, Cfap206 knockout mice, electron tomography, protein localization, Xenopus crispant larvae analysis |
Development (Cambridge, England) |
High |
32376681
|
| 2024 |
Foxj1 is expressed in olfactory sensory neurons (OSNs) in zebrafish and mice and is required for olfactory epithelium formation and olfactory cilia biogenesis; ciliary motility genes are repressed in OSNs despite Foxj1 expression; Foxj1 controls OSN-specific gene expression (including olfactory marker protein omp) and odor-evoked signal transduction, demonstrating that the canonical motile ciliogenic Foxj1 program has been repurposed for immotile olfactory cilia biogenesis and OSN differentiation. |
Zebrafish foxj1 mutants, mouse Foxj1 knockout analysis, single-cell transcriptomics, calcium imaging of odor responses, in situ hybridization |
PLoS biology |
High |
38271330
|
| 2023 |
LRRC6 facilitates active nuclear translocation of FOXJ1 in multiciliated cells; in Lrrc6 knockout mice, FOXJ1 is retained in the cytoplasm; nuclear import is blocked by INI-43 (an importin α inhibitor), demonstrating that LRRC6 promotes FOXJ1 nuclear localization via an importin α-dependent mechanism, upstream of cilia-related gene transcription. |
Lrrc6 knockout mice, proteomic and transcriptomic analyses, immunofluorescence subcellular localization, importin inhibitor (INI-43) treatment, mouse basal cell organoids |
Cell communication and signaling : CCS |
High |
37328841
|
| 2023 |
Heterozygous disruption of one Foxj1 allele in mice causes incomplete ependymal cell differentiation: reduced mature ependymal cell number, reduced motile cilia number, 12% abnormal axonemes, decreased microtubule attachment to basal bodies, random basal body orientation, loss of planar cell polarity, and disrupted unidirectional CSF flow leading to communicating hydrocephalus. |
Heterozygous Foxj1 knockout mice, immunofluorescence, transmission electron microscopy, planar cell polarity analysis, CSF flow measurement |
Cellular and molecular neurobiology |
High |
37620636
|
| 2024 |
Recombinant human FOXJ1 protein binds DNA (consensus FOX binding sequence), forms higher-order oligomers via cysteine-induced disulfide bonds (reducible by DTT), exhibits anomalous migration on denaturing gels due to polyacidic gel-shifting domains, and contains intrinsically disordered regions; the DNA-binding domain alone also binds the consensus sequence. |
Recombinant protein expression (E. coli, GST-tagged), EMSA/DNA-binding assays, denaturing gel electrophoresis, DTT reduction, codon optimization |
Protein expression and purification |
Medium |
39549898
|
| 2026 |
FOXJ1 overexpression confers docetaxel resistance in prostate cancer cells and xenografts via decreased docetaxel-mediated microtubule bundling; FOXJ1 knockdown impairs basal microtubule function, enhances taxane binding to microtubules, and increases docetaxel sensitivity; overexpression of the FOXJ1-regulated gene TPPP3 phenocopies FOXJ1 overexpression, establishing a FOXJ1 → TPPP3/microtubule dynamics → taxane resistance axis. |
In vitro FOXJ1 overexpression/knockdown in prostate cancer cells, in vivo patient-derived xenograft models, microtubule bundling assays, taxane-binding assays, TPPP3 overexpression experiments |
Nature communications |
High |
41690905
|
| 2022 |
FoxJ1 inhibits ASFV replication; overexpression of FoxJ1 upregulates type I interferon and ISG transcription induced by poly(dA:dT); FoxJ1 degrades ASFV MGF505-2R and E165R proteins via the autophagy pathway; conversely, ASFV S273R protein inhibits FoxJ1 expression, revealing a host-pathogen antagonism. |
Overexpression/knockdown in primary porcine alveolar macrophages, RT-qPCR, western blot, autophagy pathway inhibitor experiments, viral replication measurement |
Virologica Sinica |
Medium |
35513267
|
| 2013 |
In Xenopus, foxj1 knockdown abolishes cilia in brain ventricles, causing impaired CSF flow and fourth ventricle hydrocephalus, demonstrating that Foxj1-dependent motile ependymal cilia are essential for CSF circulation and maintenance of homeostatic fluid pressure during brain development. |
Xenopus morpholino knockdown, scanning electron microscopy, bead injection + video microscopy of ventricular CSF flow, gene expression analysis |
Cilia |
High |
24229449
|
| 2026 |
ChIP-seq in normal human airway epithelial cells (hAECs) defined consensus FOXJ1 and RFX binding motifs and their close proximity, suggesting functional cooperation in a transcriptional complex; combining ChIP-seq with RNA-seq from FOXJ1-PCD patients identified 683 direct FOXJ1 target genes, including 89 MCC-enriched genes (microtubule-inner proteins, dynein arm docking components) downregulated in FOXJ1-deficient cells, establishing FOXJ1 as a direct transcriptional activator of axonemal structural gene expression in human MCCs. |
ChIP-seq in human airway epithelial cells, RNA-seq from FOXJ1-PCD patient cells, motif analysis |
American journal of respiratory cell and molecular biology |
High |
42089308
|
| 2005 |
Epistasis analysis using Foxj1/inv double-mutant mice showed that the Foxj1-null random laterality phenotype is dominant over the inv-mutant mirror-image laterality phenotype; right pulmonary isomerism and absent bilateral Pitx2 expression in lateral plate mesoderm is a major phenotype of Foxj1 mutant mice, placing Foxj1 upstream of Pitx2 in the LR signaling pathway. |
Foxj1/inv double-mutant mouse generation, phenotypic analysis, Pitx2 expression analysis |
Biochemical and biophysical research communications |
Medium |
16325766
|