Affinage

FOXJ1

Forkhead box protein J1 · UniProt Q92949

Length
421 aa
Mass
45.2 kDa
Annotated
2026-04-28
85 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXJ1 is a forkhead-family transcription factor that serves as a master regulator of motile ciliogenesis across vertebrate tissues, controlling basal body docking, apical membrane organization, and axoneme assembly. FOXJ1 binds FOX consensus DNA sequences as a transcriptional activator, directly inducing a program of hundreds of cilia-associated genes (including CFAP206, CFAP157, and calpastatin), and cooperates with the co-activator RFX3 to enhance ciliated gene expression (PMID:9096351, PMID:12818891, PMID:23822649, PMID:27914912). Mechanistically, FOXJ1 promotes basal body anchoring through a calpastatin–calpain–ezrin pathway and RhoA-dependent apical actin web formation, and its nuclear translocation requires LRRC6-mediated importin-α-dependent import; upstream, FOXJ1 transcription and mRNA stability are regulated by p73, Wnt/β-catenin, Hedgehog/Shh, PITX2, IL-13/STAT6, and FTO-mediated m6A demethylation (PMID:14996907, PMID:17488776, PMID:37328841, PMID:26947080, PMID:22190638, PMID:33761320). Heterozygous loss-of-function mutations in FOXJ1 cause an autosomal-dominant motile ciliopathy featuring hydrocephalus, chronic airway disease, and laterality defects, and FOXJ1 additionally functions outside ciliated epithelia to antagonize NF-κB via IκBβ regulation in T and B cells (PMID:31630787, PMID:14963332, PMID:16002694).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Establishing that FOXJ1 is a sequence-specific DNA-binding transcriptional activator answered the fundamental question of how FOXJ1 functions molecularly — as a direct transcription factor rather than a cofactor or signaling molecule.

    Evidence In vitro DNA-binding site selection with recombinant protein, EMSA, and cotransfection activation assays

    PMID:9096351

    Open questions at the time
    • Physiological target genes in vivo not yet identified
    • No structural information on the DNA-binding domain
    • Activator versus repressor activity context-dependent
  2. 2000 High

    The Foxj1 knockout mouse revealed that FOXJ1 is essential specifically for motile (9+2) ciliogenesis but dispensable for sensory (9+0) cilia, and that the defect lies in basal body migration and apical docking rather than basal body formation per se.

    Evidence Targeted gene knockout in mice with electron microscopy across airway, ependyma, and oviduct

    PMID:10873152

    Open questions at the time
    • Molecular targets mediating basal body docking unknown
    • Whether Foxj1 is sufficient for cilia formation untested
  3. 2003 High

    Reconstitution of Foxj1 in null airway cells rescued basal body docking and axoneme growth, establishing that Foxj1 functions cell-autonomously at a late stage of ciliogenesis and is both necessary and sufficient for basal body anchoring in committed ciliated precursors.

    Evidence Gene delivery and reconstitution in Foxj1-null primary mouse airway epithelial cells with ultrastructural analysis

    PMID:12818891

    Open questions at the time
    • Downstream effector genes mediating rescue not identified
    • Whether Foxj1 acts alone or requires cofactors unknown
  4. 2004 High

    Identification of the Foxj1→calpastatin→calpain→ezrin pathway revealed the first molecular mechanism linking FOXJ1 transcriptional activity to cytoskeletal remodeling required for basal body anchoring at the apical membrane.

    Evidence Microarray of Foxj1-null lung, immunoelectron microscopy, and pharmacological rescue with calpain inhibitor in tracheal explants

    PMID:14625387 PMID:14996907

    Open questions at the time
    • Whether calpastatin is a direct transcriptional target not confirmed by ChIP
    • Only partial rescue by calpain inhibition suggests additional pathways
  5. 2004 High

    Discovery that FOXJ1 suppresses NF-κB via IκBβ in T cells, with Foxj1-null mice developing systemic inflammation and autoimmunity, revealed a non-ciliary immune-regulatory function for FOXJ1 and broadened its biological role beyond epithelial ciliogenesis.

    Evidence Foxj1 knockout mice with NF-κB transcriptional assays, T cell and B cell functional assays

    PMID:14963332 PMID:16002694

    Open questions at the time
    • Whether IκBβ is a direct transcriptional target of FOXJ1 not shown
    • Mechanism of NF-κB antagonism (transcriptional vs. protein-level) not fully resolved
    • Relevance to human immune disease unknown
  6. 2007 High

    Placing FOXJ1 upstream of RhoA activation and apical actin web formation established a second effector pathway by which FOXJ1 remodels the apical cytoskeleton for basal body docking, complementing the calpastatin–ezrin axis.

    Evidence Foxj1-null primary airway cells with RhoA activity assays and pharmacological/genetic rescue

    PMID:17488776

    Open questions at the time
    • Whether FOXJ1 activates a Rho-GEF transcriptionally or acts through another mechanism unknown
    • Relationship between RhoA and calpastatin pathways not clarified
  7. 2008 High

    Studies in zebrafish and Xenopus demonstrated that Foxj1 is both necessary and sufficient for motile cilia formation in left-right organizer structures and is a downstream target of Hedgehog, Wnt/β-catenin, and PITX2 signaling, establishing the upstream regulatory hierarchy controlling Foxj1 expression.

    Evidence Morpholino knockdown and ectopic expression in zebrafish/Xenopus; ChIP and promoter assays for PITX2 binding; epistasis with Hedgehog and Wnt

    PMID:18723525 PMID:19011629 PMID:19011630 PMID:22190638

    Open questions at the time
    • Integration of multiple upstream inputs (Shh, Wnt, PITX2) at the Foxj1 promoter not resolved
    • Whether all upstream pathways are conserved in mammals not fully tested
  8. 2010 High

    The finding that Foxj1-induced cilia attenuate Shh signaling by reducing Gli activity established a negative feedback loop where Foxj1, itself a Shh target, modulates the very pathway that activates it.

    Evidence Chick electroporation, mouse Foxj1-null analysis, and Shh signaling assays in cell lines

    PMID:21098568

    Open questions at the time
    • Mechanism by which cilia length increase attenuates Gli activity not molecularly defined
    • Generality across tissues beyond floor plate not established
  9. 2012 High

    Knock-in of Foxj1 into the Noto locus rescued nodal cilia structure but not posterior positioning, establishing the epistatic hierarchy Noto→Foxj1→Rfx3 and distinguishing FOXJ1's role in cilia assembly from planar cell polarity.

    Evidence Foxj1 cDNA knock-in into Noto locus in mouse, nodal cilia ultrastructure and flow analysis

    PMID:22357932

    Open questions at the time
    • How Noto activates Foxj1 transcription not defined
    • Whether Rfx3 is a direct Foxj1 target not shown by ChIP at this locus
  10. 2013 High

    Demonstration that FOXJ1 and RFX3 physically interact and cooperatively activate cilia gene promoters resolved how FOXJ1 achieves target gene specificity and transcriptional potency during multiciliogenesis.

    Evidence Co-immunoprecipitation, promoter assays, and gene expression analysis in human airway basal cells

    PMID:23822649

    Open questions at the time
    • Structural basis of FOXJ1–RFX3 interaction unknown
    • Genome-wide co-occupancy not mapped
  11. 2016 High

    ChIP-seq identification of Foxj1 as a direct p73 target in multiciliated cells, combined with genome-wide identification of ~326 FOXJ1-dependent ciliogenesis genes including CFAP206 and CFAP157, defined both the upstream activator and the downstream transcriptional program of FOXJ1.

    Evidence p73 ChIP-seq in murine tracheal cells; microarray of Foxj1-null fetal lungs and Noto-null embryos; KO mouse validation of CFAP targets

    PMID:26947080 PMID:27914912 PMID:27965440

    Open questions at the time
    • Which of the 326 genes are direct versus indirect FOXJ1 targets not resolved genome-wide
    • Functional hierarchy among FOXJ1 target genes not established
  12. 2019 High

    Identification of heterozygous FOXJ1 loss-of-function mutations as the cause of an autosomal-dominant motile ciliopathy in humans translated the mouse phenotype to clinical genetics, confirming haploinsufficiency as disease mechanism.

    Evidence Whole-exome/genome sequencing of patient cohort with functional validation in patient respiratory epithelial cells

    PMID:31630787

    Open questions at the time
    • Genotype-phenotype correlation across different FOXJ1 mutations incomplete
    • Whether PTK2 mislocalization is mechanistically causal or secondary unknown
  13. 2021 High

    Discovery that FTO stabilizes FOXJ1 mRNA through m6A demethylation revealed a post-transcriptional regulatory layer controlling FOXJ1 abundance, upstream of and independent from transcriptional regulation.

    Evidence FTO depletion in human airway epithelium and Xenopus with mRNA stability and m6A measurements; Fto knockout mice

    PMID:33761320

    Open questions at the time
    • Specific m6A sites on FOXJ1 mRNA responsible for destabilization not mapped
    • Which m6A reader mediates FOXJ1 mRNA decay unknown
  14. 2023 Medium

    Demonstration that LRRC6 facilitates importin-α-dependent nuclear translocation of FOXJ1 resolved a long-standing question of how cytoplasmic FOXJ1 protein accesses the nucleus to activate its target genes.

    Evidence Lrrc6 KO mice showing cytoplasmic FOXJ1 retention; pharmacological blockade with importin-α inhibitor INI-43

    PMID:37328841

    Open questions at the time
    • Direct LRRC6–FOXJ1 physical interaction not demonstrated
    • Whether LRRC6 acts as an adaptor or modifies FOXJ1 for importin recognition unknown
    • Single laboratory finding
  15. 2024 High

    Extension of Foxj1 function to olfactory sensory neuron differentiation and immotile olfactory cilia biogenesis showed that the FOXJ1 ciliogenic program is modularly repurposed, with motile cilia genes actively repressed in this context.

    Evidence Foxj1 mutant zebrafish and mouse with single-cell transcriptomics and olfactory functional assays

    PMID:38271330

    Open questions at the time
    • Mechanism of selective repression of motility genes in OSNs unknown
    • Which co-factors specify the immotile versus motile program in FOXJ1-expressing cells not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of FOXJ1 DNA binding and oligomerization, genome-wide discrimination of direct versus indirect targets, how FOXJ1 integrates multiple upstream signals at its promoter, and how the motile versus immotile cilia program is differentially specified in FOXJ1-expressing cells.
  • No crystal or cryo-EM structure of FOXJ1 or FOXJ1–DNA complex
  • Genome-wide ChIP-seq for FOXJ1 itself not reported
  • Mechanism selecting motile versus immotile cilia gene sets unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 7 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2
Partners
LEF1LRRC6PITX2RFX3

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Targeted deletion of Foxj1 (HFH-4) in mice results in complete absence of 9+2 motile cilia in airway epithelial cells, ependyma, and oviduct, while 9+0 sensory cilia (e.g., olfactory) are unaffected. Ultrastructural analysis showed that defective ciliogenesis is due to abnormal centriole migration and/or failure of apical membrane docking, indicating Foxj1 functions to direct basal body positioning and anchoring. Targeted gene knockout in mice, electron microscopy, in situ hybridization American journal of respiratory cell and molecular biology High 10873152
1997 Recombinant HFH-4 (FOXJ1) protein binds DNA with consensus sequences HWDTGTTTGTTTA or KTTTGTTGTTKTW, identified by in vitro DNA-binding site selection. HFH-4 forms specific protein-DNA complexes with promoter regions of genes including prothrombin, beta-amyloid precursor protein, CFTR, and HNF-3alpha, and acts as a potent transcriptional activator in cotransfection assays. In vitro DNA-binding site selection 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 Foxj1-null airway epithelial cells, basal bodies form and cells commit to ciliogenesis, but basal bodies are disorganized in the apical compartment and fail to dock with the apical membrane. Reconstitution of Foxj1 in null cells restored normal basal body organization, resulting in axoneme growth, demonstrating Foxj1 functions specifically in late-stage ciliogenesis to regulate basal body docking and axoneme formation. Primary mouse airway epithelial cell culture, foxj1-null cells, gene delivery/reconstitution, ultrastructural analysis American journal of physiology. Lung cellular and molecular physiology High 12818891
2004 Microarray analysis of Foxj1-null vs. wild-type pulmonary epithelium identified calpastatin (a calpain inhibitor) as a Foxj1 target; loss of Foxj1 decreased calpastatin expression, leading to increased calpain activity, degradation of ezrin, and failure of basal bodies to anchor to the apical cytoskeleton. Treatment of Foxj1-null tracheal explants with a calpain inhibitor partially restored cilia and relocalized ezrin and EBP-50, establishing a Foxj1→calpastatin→calpain→ezrin→basal body anchoring pathway. Microarray, RNase protection, immunohistochemistry, western blot, immunoelectron microscopy, pharmacological rescue with calpain inhibitor Journal of cell science High 14996907
2003 Foxj1 expression is required for apical localization of ezrin (but not moesin) in airway epithelial cells. In Foxj1-null cells, membrane-cytoskeletal and threonine-phosphorylated ezrin are decreased, and ERM-associated EBP50 and beta2 adrenergic receptor fail to localize apically, demonstrating Foxj1 differentially regulates ERM proteins to organize multi-protein complexes at apical membranes of ciliated cells. Foxj1-null mouse airway epithelial cells, immunofluorescence, western blot, fractionation Journal of cell science High 14625387
2004 Foxj1 suppresses NF-κB transcriptional activity in T cells. Foxj1-deficient T cells show increased NF-κB activity in vivo, and Foxj1 can regulate IκB proteins, particularly IκBβ. Loss of Foxj1 results in multiorgan systemic inflammation, exaggerated Th1 cytokine production, and T cell proliferation in autologous mixed lymphocyte reactions, establishing Foxj1 as an NF-κB repressor in T cells. Foxj1 knockout mice, in vitro NF-κB transcriptional assays, T cell functional assays, cytokine measurement Science (New York, N.Y.) High 14963332
2007 Foxj1 promotes RhoA and RhoB activation during ciliogenesis. Foxj1-null mice lack apical actin web formation and basal body docking, which are both rescued by RhoA activation. Foxj1 expression coincides with and is required for apical actin web formation essential for basal body docking, and Foxj1 also promotes apical ezrin localization via RhoA, placing Foxj1 upstream of RhoA in cytoskeletal remodeling during ciliogenesis. Primary mouse airway epithelial cell culture, Foxj1-null mice, actin perturbation assays, RhoA inhibition, immunofluorescence Journal of cell science High 17488776
2008 Zebrafish foxj1a, a target of Hedgehog signaling in the floor plate, acts as a master regulator of motile cilia formation. Foxj1a loss compromises assembly of motile cilia in floor plate, Kupffer's vesicle, and pronephric ducts, and its ectopic expression is sufficient to induce ectopic development of motile cilia-like structures. A paralogous gene foxj1b regulates motile cilia in the otic vesicle. Zebrafish loss-of-function (morpholino), ectopic expression assays, epistasis with Hedgehog signaling Nature genetics High 19011630
2008 Xenopus and zebrafish Foxj1 is required for formation of motile cilia at the gastrocoel roof plate (GRP) and Kupffer's vesicle that underlie left-right patterning. Microarray analysis showed Foxj1 induces cilia formation by upregulating motile cilia gene expression. Misexpression of Foxj1 is sufficient to induce ectopic GRP-like cilia formation in frog embryos. Morpholino knockdown in Xenopus/zebrafish, ectopic expression, microarray transcriptional profiling Nature genetics High 19011629
2007 IL-13 treatment of differentiated human airway epithelium decreases foxj1 expression via a STAT6-binding element in the foxj1 promoter. STAT-6 and IL-13 inhibit foxj1 expression, resulting in loss of apical basal body localization, loss of ezrin from the apical compartment, and loss of ciliated cells, establishing an IL-13/STAT6→FOXJ1 regulatory axis in airway ciliogenesis. Human airway epithelial culture, IL-13 treatment, STAT6 inhibition, promoter analysis, immunofluorescence American journal of respiratory cell and molecular biology High 17541011
2011 Wnt/β-catenin signaling directly regulates foxj1a expression and ciliogenesis in zebrafish Kupffer's vesicle. Enhancer analysis identifies Lef1/Tcf binding sites required for KV-specific foxj1a expression. Wnt signaling reduction causes shorter/fewer cilia, loss of cilia motility, and LR patterning defects that are rescued by KV-targeted foxj1a overexpression, placing Wnt/β-catenin upstream of Foxj1 in the ciliogenic hierarchy. Epistasis with FGF pathway shows Wnt acts more downstream. Zebrafish genetic/pharmacological Wnt inhibition, enhancer/promoter analysis, morpholino, KV-targeted mRNA injection, epistasis Development (Cambridge, England) High 22190638
2012 Mouse Noto acts upstream of Foxj1 in the node; Foxj1 expressed from the Noto locus restores structurally normal motile cilia in Noto-null nodes. However, Foxj1 is not sufficient for correct posterior cilia positioning on node cells (a Noto-regulated event), and Foxj1 is essential for ciliogenesis in the node upstream of Rfx3, establishing the epistatic order Noto→Foxj1→Rfx3 in nodal ciliogenesis. Knock-in of Foxj1 cDNA into Noto locus, Foxj1-null mouse analysis, nodal cilia ultrastructure and flow analysis Development (Cambridge, England) High 22357932
2013 FOXJ1 and RFX3 physically interact (co-immunoprecipitation) and cooperatively induce cilia gene expression in human airway basal cells. FOXJ1 transfection activates ciliated gene promoters and induces RFX3 expression; RFX3 alone cannot induce cilia genes. The combination of FOXJ1+RFX3 enhances ciliated gene promoter activity and mRNA expression beyond FOXJ1 alone, establishing RFX3 as a co-activator of FOXJ1. Human airway basal cell transfection, air-liquid interface differentiation, promoter assays, co-immunoprecipitation, TaqMan PCR Respiratory research High 23822649
2016 p73 directly regulates Foxj1 transcription in multiciliated cells. ChIP-seq in murine tracheal cells identifies Foxj1 as a direct p73 (and p63) target gene. Loss of p73 impairs MCC differentiation, causing hydrocephalus, hippocampal dysgenesis, sterility, and chronic airway inflammation, establishing p73 as an upstream transcriptional activator of Foxj1 in the multiciliogenesis program. p73 knockout mice, ChIP-seq, gene expression analysis, functional phenotypic characterization Cell reports High 26947080
2021 The m6A demethylase FTO stabilizes FOXJ1 mRNA by removing m6A modifications. FTO depletion leads to FOXJ1 mRNA destabilization and severe loss of ciliated cells in primary human airway epithelium, with increase in goblet cells. In Xenopus, Foxj1 is a phenocritical FTO target for motile ciliogenesis, establishing an FTO→FOXJ1 mRNA stability axis upstream of the ciliogenic program. FTO depletion in Xenopus (morpholino), human airway epithelium (siRNA/KD), mRNA stability assays, m6A analysis, Fto knockout mice Developmental cell High 33761320
2010 Foxj1 expression in the neural tube (chick and mouse floor plate) is regulated by Shh signaling, is sufficient to increase cilia length in neuroepithelial cells when ectopically expressed, and attenuates intracellular Shh signaling by decreasing Gli protein activity in a cilia-dependent manner, establishing a feedback mechanism where Foxj1-induced cilia modulate Shh signal transduction. Chick electroporation, mouse Foxj1-null analysis, Shh signaling assays, ectopic expression in Shh-responsive cell line Development (Cambridge, England) High 21098568
2005 Foxj1 restrains B cell activation intrinsically by antagonizing NF-κB and its target IL-6. Foxj1 deficiency in B cells results in spontaneous and accentuated germinal center formation, pathogenic autoantibodies, and accentuated immunization responses, correlating with a requirement for Foxj1 to regulate the inhibitory NF-κB component IκBβ. Foxj1-deficient B cell analysis, NF-κB activity assays, germinal center formation, autoantibody detection Journal of immunology (Baltimore, Md. : 1950) High 16002694
2008 PITX2 binds the FoxJ1 promoter (shown by chromatin immunoprecipitation) and activates FoxJ1 expression. Lef-1 and β-catenin interact with PITX2 to synergistically regulate the FoxJ1 promoter. FoxJ1 physically interacts with the PITX2 homeodomain to synergistically regulate FoxJ1 expression, providing a positive autoregulatory feedback mechanism. The ARS-associated PITX2 T68P mutant interacts with FoxJ1 but cannot activate the FoxJ1 promoter. Chromatin immunoprecipitation, cotransfection promoter assays, protein-protein interaction (co-IP/pulldown), PITX2 transgenic mouse fibroblasts Human molecular genetics High 18723525
2019 De novo heterozygous loss-of-function mutations in FOXJ1 cause an autosomal-dominant motile ciliopathy with hydrocephalus, chronic airway disease, and left/right body asymmetry randomization. Mutant respiratory epithelial cells have reduced cilia number per cell, impaired fluid flow, and mislocalized basal bodies. The focal adhesion protein PTK2 displays aberrant cytoplasmic localization in mutant cells. Whole-exome/genome sequencing, high-speed video microscopy, TEM, immunofluorescence in patient cells American journal of human genetics High 31630787
2023 Heterozygous disruption of one Foxj1 allele in mice leads to incomplete ependymal cell differentiation with decreased mature ependymal cell number, decreased motile cilia number, abnormal axonemes in 12% of cilia, decreased microtubule attachment to basal bodies, random localization and orientation of basal body patches, loss of planar cell polarity, and disruption of unidirectional CSF flow causing communicating hydrocephalus. Foxj1 heterozygous knockout mice, immunofluorescence, electron microscopy, CSF flow analysis Cellular and molecular neurobiology High 37620636
2005 Foxj1 regulates thymic egress of T cells. CD2-Foxj1 transgenic mice exhibit peripheral T cell lymphopenia associated with accumulation of mature single-positive thymocytes. Transgenic thymocytes demonstrate impaired thymic exodus in response to CCL19, apparently independent of CCR7, S1P1, and NF-κB, demonstrating a role for Foxj1 in thymocyte egress. CD2-Foxj1 transgenic mice on MRL/lpr background, adoptive transfer, chemokine migration assays Journal of immunology (Baltimore, Md. : 1950) Medium 16339515
2012 In Xenopus, ATP4a is required for Wnt/β-catenin-regulated Foxj1 induction in the superficial mesoderm. Gene knockdown or pharmacological inhibition of ATP4 compromises organ situs, asymmetric marker gene expression, leftward flow, and Foxj1 expression. ATP4 acts upstream of Wnt/β-catenin→Foxj1 induction and Wnt/PCP-dependent cilia polarization in symmetry breaking. Xenopus morpholino knockdown, pharmacological inhibition, gene expression analysis, cilia analysis Cell reports Medium 22832275
2014 FOXJ1 overexpression prevents cigarette smoke extract (CSE)-mediated inhibition of cilia growth in human airway basal cell ALI cultures, partially reversing CSE-induced suppression of cilia-related genes involved in intraflagellar transport, motility, structural integrity, and basal body development. Human airway basal cell ALI cultures, lentiviral FOXJ1 overexpression, cilia length measurement, gene expression profiling American journal of respiratory cell and molecular biology Medium 24828273
2004 Estradiol (E2) induces Foxj1 expression in rat oviduct infundibulum/ampulla via estrogen receptor, and Foxj1 expression precedes cilia appearance. Foxj1-deficient mice completely lack oviductal cilia, demonstrating Foxj1 is directly required for oviductal ciliogenesis, while ERα signaling is not essential (ERα-deficient mice retain cilia). Rat oviduct organ culture with E2, ER antagonist, Foxj1-null and ERα-null mouse analysis, immunohistochemistry Journal of molecular endocrinology Medium 15171704
2023 LRRC6 facilitates active nuclear translocation of FOXJ1. In Lrrc6 knockout mice, FOXJ1 is retained in the cytoplasm; LRRC6 expression promotes FOXJ1 nuclear translocation, which is blocked by INI-43 (an importin α inhibitor), suggesting an importin α-dependent nuclear import pathway for FOXJ1 regulated by LRRC6. Lrrc6 KO mice, immunofluorescence, pharmacological inhibition (INI-43), transcriptomic analysis of cilia genes Cell communication and signaling : CCS Medium 37328841
2016 Microarray screening of Foxj1-deficient vs. wild-type fetal mouse lungs and Noto-null embryos identified 326 candidate FOXJ1-dependent ciliogenesis-associated genes, including Cfap206, Cfap157, Fam183b, and 1700012B09Rik, providing the downstream genetic program of motile ciliogenesis regulated by FOXJ1 in mammalian tissues. Microarray of Foxj1-deficient and stage-matched fetal mouse lungs and node embryos, functional validation of selected targets Developmental biology Medium 27914912
2016 CFAP157, a FOXJ1 target gene, encodes a protein localizing to basal bodies that interacts with tubulin and the centrosomal protein CEP350. Cfap157 knockout mice are male-infertile with flagellar axoneme defects including supernumerary axonemal profiles and ectopic accessory structures, establishing CFAP157 as a FOXJ1 effector required for spermiogenesis. Foxj1-dependent expression analysis, Cfap157 KO mice, protein-protein interaction (pulldown), immunofluorescence, electron microscopy Development (Cambridge, England) Medium 27965440
2020 CFAP206, a FOXJ1 target gene, encodes a protein localizing to the basal body and axoneme of motile cilia. Cfap206 knockout mice show male infertility, hydrocephalus, and impaired mucociliary clearance. Electron tomography of knockout sperm flagella indicates a role in radial spoke formation, consistent with FAP206 function in Tetrahymena. Foxj1-dependent expression analysis, Cfap206 KO mice and Xenopus crispants, electron tomography, ciliary beat frequency measurement Development (Cambridge, England) Medium 32376681
2023 A truncating FOXJ1 variant (p.Glu267Glyfs*12) fails to induce ectopic cilia in frog epidermis in vivo and fails to activate the ADGB promoter (a downstream FOXJ1 target) in transactivation assays, demonstrating loss of transcriptional transactivation function associated with congenital heart defects in a patient. Xenopus ectopic cilia assay, in vitro promoter transactivation, exome sequencing Human molecular genetics Medium 37158461
2024 Recombinant FOXJ1 protein binds DNA at the FOX consensus sequence, forms cysteine-dependent higher-order oligomers via disulfide bridges, contains polyacidic gel-shifting domains at the N- and C-termini causing anomalous electrophoretic migration, and harbors intrinsically disordered regions. Recombinant protein expression, DNA-binding assay, DTT reduction of oligomers, SDS-PAGE anomalous migration analysis Protein expression and purification Medium 39549898
2024 In zebrafish and mice, Foxj1 is expressed in olfactory sensory neurons (OSNs) and is required for olfactory cilia biogenesis and for differentiation of OSNs themselves, including regulation of olfactory marker protein (omp) expression. Ciliary motility genes are repressed in OSNs despite Foxj1 expression, showing the motile ciliogenic program is repurposed for immotile olfactory cilia. Zebrafish Foxj1 mutants, mouse Foxj1 analysis, single-cell transcriptomics, odor response assays, in situ hybridization PLoS biology High 38271330
2026 FOXJ1 overexpression in prostate cancer cells confers docetaxel resistance by decreasing docetaxel-mediated microtubule bundling, while FOXJ1 knockdown impairs basal microtubule function, enhances taxane binding to microtubules, and increases docetaxel sensitivity. TPPP3, a microtubule-associated FOXJ1-regulated gene, has similar effects on taxane resistance when overexpressed. Prostate cancer PDX in vivo models, FOXJ1 overexpression/knockdown in vitro and in vivo, microtubule bundling assays, taxane binding assays Nature communications High 41690905
2018 FoxJ1 is required during embryonic spinal cord development for progenitor proliferation and cell fate determination, and FoxJ1 loss results in formation of adult ependymal cells with impaired stem cell potential and inability to respond to spinal cord injury. FoxJ1 fate-mapping mouse lines, FoxJ1 knock-in mice, spinal cord injury model, immunofluorescence, proliferation assays Experimental cell research Medium 29689278
2013 In Xenopus, foxj1 knockdown (morpholino) in the CNS causes absence of ependymal cilia, impaired CSF flow, and fourth ventricle hydrocephalus, establishing that motile ependymal cilia driven by Foxj1 are essential for CSF circulation and maintenance of homeostatic fluid pressure in the brain. Xenopus foxj1 morpholino knockdown, scanning electron microscopy, bead injection and video microscopy of CSF flow Cilia Medium 24229449
2005 In Foxj1/inv double mutant mice, the random laterality phenotype of Foxj1 is dominant over the reversal-of-situs phenotype of inv, and right pulmonary isomerism (due to absent bilateral Pitx2 expression in lateral plate mesoderm) is a major phenotype of Foxj1-null mice. This epistatic analysis places Foxj1 upstream of Pitx2 in left-right axis determination. Double mutant mouse analysis (Foxj1 × inv), lung morphology, in situ hybridization for Pitx2 Biochemical and biophysical research communications Medium 16325766

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Foxj1 transcription factors are master regulators of the motile ciliogenic program. Nature genetics 376 19011630
2000 Ciliogenesis and left-right axis defects in forkhead factor HFH-4-null mice. American journal of respiratory cell and molecular biology 289 10873152
2008 The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos. Nature genetics 268 19011629
2003 Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells. American journal of physiology. Lung cellular and molecular physiology 172 12818891
2007 RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1. Journal of cell science 171 17488776
2019 De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left/Right Body Asymmetry. American journal of human genetics 156 31630787
2012 Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers. Oncogene 138 22945654
1999 Forkhead transcription factor HFH-4 expression is temporally related to ciliogenesis. American journal of respiratory cell and molecular biology 130 10423398
2016 p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network. Cell reports 123 26947080
2004 Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells. Journal of cell science 117 14996907
2004 Modulation of Th1 activation and inflammation by the NF-kappaB repressor Foxj1. Science (New York, N.Y.) 111 14963332
2011 Wnt/β-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer's vesicle. Development (Cambridge, England) 106 22190638
1997 The winged helix transcription factor HFH-4 is expressed during choroid plexus epithelial development in the mouse embryo. Proceedings of the National Academy of Sciences of the United States of America 89 9096351
2003 Foxj1 is required for apical localization of ezrin in airway epithelial cells. Journal of cell science 83 14625387
2010 Foxj1 regulates floor plate cilia architecture and modifies the response of cells to sonic hedgehog signalling. Development (Cambridge, England) 82 21098568
2007 IL-13 regulates cilia loss and foxj1 expression in human airway epithelium. American journal of respiratory cell and molecular biology 79 17541011
2013 RFX3 modulation of FOXJ1 regulation of cilia genes in the human airway epithelium. Respiratory research 78 23822649
2007 A transgenic FOXJ1-Cre system for gene inactivation in ciliated epithelial cells. American journal of respiratory cell and molecular biology 74 17255554
2014 FOXJ1 prevents cilia growth inhibition by cigarette smoke in human airway epithelium in vitro. American journal of respiratory cell and molecular biology 73 24828273
2012 ATP4a is required for Wnt-dependent Foxj1 expression and leftward flow in Xenopus left-right development. Cell reports 73 22832275
2001 Effects of paramyxoviral infection on airway epithelial cell Foxj1 expression, ciliogenesis, and mucociliary function. The American journal of pathology 72 11733356
1999 HNF-3/forkhead homologue-4 (HFH-4) is expressed in ciliated epithelial cells in the developing mouse lung. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 72 10330459
2010 Goblet cells are derived from a FOXJ1-expressing progenitor in a human airway epithelium. American journal of respiratory cell and molecular biology 64 20539013
2004 Role of foxj1 and estrogen receptor alpha in ciliated epithelial cell differentiation of the neonatal oviduct. Journal of molecular endocrinology 58 15171704
2013 Ciliogenesis and cerebrospinal fluid flow in the developing Xenopus brain are regulated by foxj1. Cilia 49 24229449
2012 Evolutionarily ancient association of the FoxJ1 transcription factor with the motile ciliogenic program. PLoS genetics 48 23144623
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