Affinage

PAX9

Paired box protein Pax-9 · UniProt P55771

Length
341 aa
Mass
36.3 kDa
Annotated
2026-04-29
100 papers in source corpus 28 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAX9 is a paired-domain transcription factor that controls organogenesis of teeth, palate, thymus, pharyngeal arch derivatives, taste papillae, and the vertebral column by establishing mesenchymal and epithelial competence through direct transcriptional regulation of key developmental signaling networks. PAX9 binds DNA through its paired domain to activate targets such as Bmp4, Msx1, Bapx1, and Osr2 promoters, and represses Wnt antagonists Dkk1/Dkk2 to sustain canonical Wnt signaling during palatogenesis (PMID:9732271, PMID:16651263, PMID:28893947, PMID:12490554). It forms functional protein complexes with MSX1, OSR2, and the NuRD co-repressor complex, and acts at distal enhancers where NuRD recruitment maintains a repressed chromatin state that restricts differentiation gene expression (PMID:15721141, PMID:21420399, PMID:34341073). Loss-of-function mutations in the paired domain that abolish DNA binding cause oligodontia/tooth agenesis through haploinsufficiency, while complete Pax9 deficiency arrests tooth development at the bud stage, produces cleft palate, thymus aplasia, and vertebral defects (PMID:9732271, PMID:14607846, PMID:10556064, PMID:12032925).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Establishing that PAX9 is a direct DNA-binding transcription factor resolved whether the paired domain was functionally active, confirming PAX9 as a sequence-specific DNA-binding protein recognizing paired-domain consensus sites.

    Evidence EMSA with purified PAX9 paired domain on the e5 sequence from the even-skipped promoter

    PMID:7649395

    Open questions at the time
    • Endogenous genomic targets not identified
    • No information on transcriptional output (activation vs. repression)
  2. 1996 High

    Demonstrating that PAX9 possesses C-terminal transactivation domains whose potency differs between alternatively spliced isoforms established PAX9 as a transcriptional activator and revealed auto-inhibition by its N-terminal paired domain.

    Evidence Reporter assays with domain deletions of zebrafish Pax9a/Pax9b isoforms in transfected cells

    PMID:8900176

    Open questions at the time
    • Mammalian isoform differences not tested
    • Endogenous target promoters not examined
  3. 1998 High

    Knockout of Pax9 in mice revealed it is essential for tooth development beyond the bud stage and required for mesenchymal expression of Bmp4, Msx1, and Lef1, establishing Pax9 as the master regulator of tooth mesenchyme inductive capacity.

    Evidence Gene targeting (Pax9 knockout mouse) with histology and in situ hybridization

    PMID:9732271

    Open questions at the time
    • Direct vs. indirect transcriptional regulation of Bmp4/Msx1 not distinguished
    • Molecular mechanism of bud-stage arrest unclear
  4. 1999 High

    Double-mutant analysis of Pax1 and Pax9 revealed synergistic and redundant roles in vertebral column chondrogenesis, showing these paralogs jointly control sclerotomal cell proliferation, survival, and Sox9/ColII expression.

    Evidence Pax1/Pax9 double-mutant mice with BrdU, TUNEL, and in situ hybridization

    PMID:10556064

    Open questions at the time
    • Individual gene contributions to sclerotome specification not fully separated
    • Direct transcriptional targets in sclerotome not identified
  5. 2002 High

    Analysis of Pax9-null thymus demonstrated Pax9 is required for thymic migration and full thymopoiesis, extending its role beyond skeletal/dental tissues to immune organ development.

    Evidence Pax9 knockout mouse with immunostaining and RT-PCR for TCR chains in thymic anlage

    PMID:11932925

    Open questions at the time
    • Direct targets of Pax9 in thymic epithelium unknown
    • Mechanism of migration failure not resolved
  6. 2003 High

    Identification of Bapx1 as a direct transcriptional target and recruitment of the co-repressor PLU-1/KDM5B through a VP motif established that PAX9 can function as both an activator (Bapx1 promoter) and a modular repressor depending on co-factor context.

    Evidence Promoter transactivation/ChIP for Bapx1; yeast two-hybrid, Co-IP, mutagenesis, and reporter assays for PLU-1 interaction

    PMID:12490554 PMID:12657635

    Open questions at the time
    • Genome-wide identification of co-repressor vs. co-activator target sets not performed
    • Endogenous relevance of PLU-1 interaction in developmental tissues not shown
  7. 2003 High

    Functional characterization of disease-causing paired-domain mutations (219InsG, R28P) demonstrated that loss of DNA binding without dominant-negative effects establishes haploinsufficiency as the pathogenic mechanism for PAX9-associated oligodontia.

    Evidence EMSA, reporter assays, immunolocalization, and co-transfection dominance tests with mutant PAX9 proteins

    PMID:14607846 PMID:14689302

    Open questions at the time
    • Not all known mutations tested
    • In vivo confirmation of haploinsufficiency mechanism in knock-in models lacking
  8. 2005 High

    Direct physical interaction between Pax9 and Msx1 proteins established a cooperative transcription factor complex in tooth mesenchyme, and upstream regulation by Gli3/Shh placed Pax9 within the Hedgehog signaling hierarchy in a tissue-dependent manner.

    Evidence Co-IP and GST pulldown for Pax9-Msx1; Gli3/Shh genetic epistasis in mouse limb and somite

    PMID:15721141 PMID:16169709

    Open questions at the time
    • Structural basis of Pax9-Msx1 interaction unknown
    • Whether Gli3 directly regulates Pax9 transcription not determined
  9. 2006 High

    Demonstrating that PAX9 directly activates Msx1 and Bmp4 promoters, and that the PAX9-MSX1 protein complex synergistically enhances this activation, defined the core transcriptional circuit (PAX9→MSX1→BMP4) driving tooth mesenchyme specification.

    Evidence Luciferase reporter assays, EMSA, and Co-IP with wild-type and L21P/I87F mutant PAX9

    PMID:16479262 PMID:16651263

    Open questions at the time
    • ChIP-seq for genome-wide PAX9 binding in tooth mesenchyme not yet performed at this stage
    • Stoichiometry of PAX9-MSX1 complex unknown
  10. 2009 High

    Comprehensive analysis of eight paired-domain mutations revealed a spectrum from loss of DNA binding to a dominant-negative mechanism disrupting PAX9-MSX1 synergy, demonstrating multiple pathogenic routes converging on impaired transactivation of Msx1/Bmp4.

    Evidence EMSA, Co-IP, reporter assays, and structural modeling across eight missense mutations

    PMID:19429910

    Open questions at the time
    • Dominant-negative mechanism identified for only one mutation
    • In vivo validation of dominant-negative pathogenesis absent
  11. 2010 High

    Genetic interaction of Pax9 and Msx1 in vivo demonstrated their cooperative control of Fgf3/Fgf10 and Bmp signaling for incisor development, with transgenic BMP4 partially rescuing double-heterozygous defects and positioning the Pax9-Msx1 axis upstream of FGF and BMP pathways.

    Evidence Pax9+/-;Msx1+/- double heterozygous mice with BrdU proliferation, in situ hybridization, and K14-Bmp4 transgenic rescue

    PMID:20123092

    Open questions at the time
    • Whether Pax9-Msx1 directly regulates Fgf3/Fgf10 promoters not tested
    • Molar vs. incisor differences in pathway requirement not fully explored
  12. 2013 High

    Conditional deletion and knock-in rescue experiments placed Osr2 directly downstream of Pax9 during palatogenesis, demonstrating that Pax9 governs a transcriptional network (including Bmp4, Fgf10, Msx1, Osr2) essential for palatal shelf morphogenesis.

    Evidence Conditional Pax9 knockout in palatal mesenchyme with Pax9Osr2KI rescue allele, in situ hybridization

    PMID:24173808

    Open questions at the time
    • Whether Pax9 directly binds Osr2 regulatory regions not shown at this stage
    • Post-transcriptional regulation in palate not explored
  13. 2017 High

    ChIP-qPCR demonstrated direct PAX9 binding at Dkk1, Dkk2, Wnt9b, and Wnt3 loci, and genetic rescue by Dkk1 reduction or Wise inactivation established that Pax9 sustains canonical Wnt signaling during palatogenesis by repressing Wnt antagonists; separately, Pax9 was placed upstream of Eda/Edar signaling specifically in palate.

    Evidence ChIP-qPCR in palatal tissue; Pax9-/-;Dkk1+/- and Pax9-/-;Wise-/- double-mutant genetic rescues; anti-EDAR agonist antibody in utero rescue

    PMID:28692808 PMID:28813171 PMID:28893947

    Open questions at the time
    • Whether Pax9 directly represses Dkk1/Dkk2 transcription vs. indirect mechanism not fully resolved
    • Eda/Edar rescue limited to single study
  14. 2017 Medium

    Conditional Pax9 deletion in oesophageal/tongue epithelium revealed a tumor-suppressive role: Pax9 loss promotes cell proliferation, delays differentiation, and enhances carcinogen-induced squamous cell carcinogenesis, extending Pax9 function to epithelial homeostasis and cancer suppression.

    Evidence Conditional knockout mouse with NMBA carcinogen treatment, immunohistochemistry, promoter methylation analysis in human OSCC

    PMID:29055049

    Open questions at the time
    • Direct transcriptional targets mediating tumor suppression not identified
    • Human functional validation limited to methylation correlation
  15. 2019 High

    Genetic interaction with Tbx1 in the pharyngeal endoderm demonstrated that Pax9 contributes to cardiovascular patterning (4th pharyngeal arch artery), broadening its developmental role to pharyngeal arch-derived cardiovascular structures.

    Evidence Tbx1+/-;Pax9+/- double heterozygous mice with Pax9Cre-based tissue mapping and transcriptomics

    PMID:31444215

    Open questions at the time
    • Direct transcriptional targets shared by Tbx1 and Pax9 not identified
    • Physical interaction between Tbx1 and Pax9 proteins not tested
  16. 2021 High

    Genome-wide analysis in cancer cells revealed PAX9 occupies distal enhancers where it recruits the NuRD complex to maintain a repressed chromatin state, with PAX9 depletion converting poised enhancers to active ones driving neural differentiation programs — establishing PAX9 as a chromatin-level transcriptional repressor beyond its classical developmental activator role.

    Evidence CRISPR dropout screen, ChIP-seq, ATAC-seq, Co-IP for PAX9-NuRD, HDAC inhibitor treatment in SCLC cells

    PMID:34341073

    Open questions at the time
    • Whether NuRD interaction is relevant in normal developmental tissues not tested
    • Structural basis of PAX9-NuRD recruitment unknown
    • Relationship between enhancer repression and tumor-suppressive function not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the genome-wide direct target repertoire of PAX9 in primary developmental tissues (tooth mesenchyme, palatal mesenchyme, thymic epithelium) via ChIP-seq; the structural basis of PAX9 interactions with MSX1, OSR2, and NuRD; whether the NuRD-mediated enhancer repression mechanism operates during normal organogenesis; and how PAX9 switches between transcriptional activation and repression at different loci.
  • No genome-wide PAX9 ChIP-seq in primary developmental tissues published
  • Structural basis of PAX9 co-factor selectivity unknown
  • Mechanism of context-dependent activator-to-repressor switching unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 8 GO:0140110 transcription regulator activity 5
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 1
Partners
CHD4HDAC1KDM5BMSX1OSR2TBX1
Complex memberships
NuRD complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 PAX9 protein can bind to the e5 sequence from the Drosophila even-skipped promoter, a paired domain recognition sequence also recognized by PAX1, demonstrating direct DNA-binding activity of the paired domain. DNA-binding assay (gel mobility shift / EMSA) Developmental biology High 7649395
1996 Zebrafish Pax9 encodes two alternatively spliced isoforms (Pax9a and Pax9b) with distinct C-terminal transactivating domains of different potency; the N-terminal region including the paired domain exerts a negative influence on transactivation activity, and both isoforms can activate promoters containing paired domain binding sites at low expression levels. Transcriptional reporter assay, alternative splicing analysis, domain deletion/overexpression in cell transfection The Journal of biological chemistry High 8900176
1998 Pax9 is essential for tooth development beyond the bud stage; in Pax9-deficient mice, tooth development arrests at the bud stage, and Pax9 is required for mesenchymal expression of Bmp4, Msx1, and Lef1, indicating Pax9 establishes the inductive capacity of the tooth mesenchyme. Gene targeting (knockout mouse), in situ hybridization, histological analysis Genes & development High 9732271
1999 Pax1 and Pax9 act synergistically and redundantly during vertebral column development; double homozygous Pax1/Pax9 mutants completely lack vertebral bodies and intervertebral discs, with defects traced to reduced cell proliferation in ventromedial sclerotomes and subsequent increased apoptosis, and loss of Sox9 and Collagen II expression indicating failure of chondrogenesis. Genetic epistasis (double mutant mouse), BrdU labeling, TUNEL apoptosis assay, in situ hybridization Development (Cambridge, England) High 10556064
2003 Pax1 and Pax9 directly transactivate the Bapx1 promoter and physically interact with Bapx1 promoter regulatory sequences; overexpression of Pax1 in chick presomitic mesoderm can substitute for Shh to induce Bapx1 expression and chondrogenic differentiation, identifying Bapx1 as a direct transcriptional target of Pax1/Pax9. Retroviral overexpression in chick, double-mutant mouse analysis, promoter transactivation assay, ChIP (physical interaction with promoter region) Development (Cambridge, England) High 12490554
2003 PAX9 interacts physically with PLU-1 (KDM5B) via a conserved VP motif; co-expression of PLU-1 with PAX9 significantly enhances transcriptional repression, identifying PLU-1 as a transcriptional co-repressor of PAX9, and mutation of the VP motif in PAX9 abolishes this co-repression. Yeast two-hybrid screen, co-immunoprecipitation, site-directed mutagenesis of binding motif, reporter transcription assay The Journal of biological chemistry High 12657635
2003 The frameshift mutation 219InsG in the PAX9 paired domain abolishes DNA binding to e5 and CD19-2(A-ins) recognition sequences, eliminates transcriptional activation, and alters nuclear localization of the mutant protein; importantly, the mutant does not exert a dominant-negative effect on wild-type PAX9 DNA binding or transactivation. EMSA (gel shift), co-transfection reporter assay, immunolocalization, Western blot The Journal of biological chemistry High 14607846
2003 The R28P missense mutation in the N-terminal subdomain of the PAX9 paired domain dramatically reduces DNA binding of the paired domain to double-stranded DNA targets, supporting loss-of-function/haploinsufficiency as the pathogenic mechanism for oligodontia. Paired domain DNA-binding assay (gel shift with purified protein) Human genetics High 14689302
2005 Pax9 physically interacts with Msx1 protein in vivo and in vitro; co-immunoprecipitation and GST pull-down assays demonstrate a direct physical association between Pax9 and Msx1 in the developing tooth mesenchyme context. Co-immunoprecipitation, GST pull-down assay Archives of oral biology High 15721141
2005 Pax9 expression in the anterior limb mesenchyme is regulated downstream of Gli3; in Gli3 null (extra-toes) mice Pax9 expression is lost from the anterior limb, and Shh-Gli3 epistasis experiments show Pax9 regulation by Shh/Gli3 is context-dependent (differs between limb and somite). Genetic epistasis (Gli3 mutant and Shh;Gli3 double mutant mice), Shh bead implantation in chick, in situ hybridization Mechanisms of development High 16169709
2006 PAX9 directly regulates Msx1 expression and forms a protein complex with Msx1 to enhance transactivation of both Msx1 and Bmp4 promoters; the T62C (L21P) missense mutation in the PAX9 paired domain abolishes DNA binding and transactivation of Msx1 and Bmp4 promoters while retaining ability to bind Msx1 protein, demonstrating paired domain DNA binding is essential for Bmp4 regulation. Promoter transactivation reporter assay, EMSA, co-immunoprecipitation, site-directed mutagenesis The Journal of biological chemistry High 16651263
2006 The Ile87Phe missense mutation within the C-terminal subdomain of the PAX9 paired domain abolishes binding to e5 and CD19-2(A-ins) DNA recognition sequences and does not affect nuclear localization or Msx1 protein interaction, demonstrating selective loss of DNA-binding function. Gel-shift assay (EMSA), immunolocalization, cell fractionation, co-immunoprecipitation European journal of human genetics : EJHG High 16479262
2008 Novel PAX9 missense mutations G6R and S43K in the paired domain both reduce DNA binding (S43K more severely than G6R) and reduce transcriptional activation of the Bmp4 promoter; severity of tooth agenesis in patients correlates with degree of DNA-binding impairment. Gel shift and super shift assay, luciferase reporter assay, immunofluorescence, immunoblotting Cells, tissues, organs High 18701815
2009 Structural and functional analysis of eight PAX9 paired domain missense mutations shows that most impair DNA binding and transcriptional activation of Msx1 and Bmp4 promoters; all mutant proteins retain nuclear localization and Msx1 interaction; one mutant (showing no DNA-binding loss) instead exhibits dominant-negative effect on wild-type PAX9 synergism with MSX1, revealing a distinct pathogenic mechanism. Subcellular localization, co-immunoprecipitation, EMSA (DNA-binding assay), luciferase reporter assay, structural modeling Human molecular genetics High 19429910
2010 Pax9 and Msx1 interact genetically in vivo; double heterozygous Pax9;Msx1 mutants exhibit missing lower incisors with reduced mesenchymal Fgf3 and Fgf10 expression, reduced Shh and Bmp2, and reduced cell proliferation; transgenic BMP4 expression partly rescues this phenotype, placing Pax9-Msx1 interaction upstream of Fgf3/Fgf10 and Bmp4 during incisor development. Double heterozygous mouse genetics, in situ hybridization, BrdU cell proliferation, transgenic rescue Developmental biology High 20123092
2011 Osr2 acts downstream of Pax9 in tooth mesenchyme; endogenous Osr2 expression is downregulated in Pax9-deficient mice; Osr2 forms stable protein complexes with Msx1 and weak complexes with Pax9 in co-transfected cells; and Osr2 expression from the Pax9 locus suppresses supernumerary tooth formation in Osr2 mutants. Knock-in mouse genetics, co-immunoprecipitation, in situ hybridization, genetic rescue experiment Developmental biology High 21420399
2013 Pax9 regulates a molecular network during palate development: tissue-specific deletion of Pax9 in palatal mesenchyme reduces Bmp4, Fgf10, Msx1, and Osr2 expression; restoration of Osr2 from the Pax9 locus rescues posterior palate morphogenesis in Pax9 mutants, placing Osr2 directly downstream of Pax9 in palatogenesis. Conditional knockout, knock-in rescue (Pax9Osr2KI allele), in situ hybridization, RT-PCR Development (Cambridge, England) High 24173808
2014 A G-quadruplex structure in PAX9 intron 1, located near the exon 1 boundary, enhances splicing efficiency of PAX9 intron 1; mutations abolishing G-quadruplex formation dramatically reduce splicing efficiency, and stabilization of the quadruplex with ligand 360A further increases splicing. Circular dichroism (CD) spectroscopy, validated double-reporter splicing assay, qPCR, site-directed mutagenesis of G-quadruplex, pharmacological stabilization Human genetics High 25204874
2014 Pax9 acts upstream of Pax1 and Sox9 in the expanding taste progenitor field of the circumvallate papilla; Pax9-deficient mice show complete arrest of circumvallate papilla development with loss of K8 and Prox1 in taste bud progenitors and progressive differentiation into epidermal-like epithelium; Pax9 is also required for soft palate taste placode induction but is dispensable for ectoderm-derived fungiform taste buds. Conditional and constitutive knockout mouse, immunostaining, in situ hybridization, lineage analysis PLoS genetics High 25299669
2017 Pax9 regulates palatogenesis through the canonical Wnt signaling pathway; Pax9-deficient embryos show reduced Axin2 expression, increased Dkk2, and reduced active β-catenin; genetic inactivation of Wise (a Wnt antagonist) rescues palatal shelf elevation and hyaluronic acid accumulation in Pax9-deficient mice. Conditional knockout, genetic double mutant rescue, Western blot for active β-catenin, in situ hybridization, histochemistry Journal of dental research High 28692808
2017 Pax9 inhibits Dkk1/Dkk2 expression to maintain Wnt signaling during palatogenesis; genetic reduction of Dkk1 corrects secondary palatal clefts in Pax9-null mice; ChIP-qPCR shows Pax9 directly binds genomic regions near the transcription start sites of Dkk1 and Dkk2, as well as near Wnt9b and Wnt3 loci. Genetic epistasis (Pax9-/-;Dkk1+/- mice), ChIP-qPCR, gene expression analysis Development (Cambridge, England) High 28893947 32390226
2017 Pax9 acts upstream of the Eda/Edar signaling pathway during palatogenesis; intravenous delivery of an anti-EDAR agonist antibody resolves cleft palate defects in Pax9-/- embryos in utero without correcting tooth, thymus, or parathyroid defects, demonstrating a unique Pax9–Eda/Edar relationship specific to palatogenesis. In utero antibody delivery in Pax9-/- mice, gene expression profiling, immunostaining Journal of dental research Medium 28813171
2017 Pax9 deficiency in mouse oesophagus promotes cell proliferation and delays differentiation; Pax9 loss promotes carcinogen-induced squamous cell carcinogenesis in tongue, oesophagus, and forestomach, and PAX9 downregulation in human OSCC is associated with promoter hypermethylation. Conditional knockout mouse, carcinogen treatment (NMBA), immunohistochemistry, gene expression profiling, promoter methylation analysis The Journal of pathology Medium 29055049
2019 Pax9 interacts genetically with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis; Tbx1/Pax9 double heterozygous mice show significantly increased incidence of interrupted aortic arch; using a Pax9Cre allele, the site of Tbx1-Pax9 genetic interaction was mapped to the pharyngeal endoderm. Double heterozygous mouse genetics, Cre-based lineage/conditional analysis (Pax9Cre allele), transcriptome analysis Development (Cambridge, England) High 31444215
2021 PAX9 occupies distal enhancer elements in SCLC cells and represses nearby gene expression by restricting enhancer activity; PAX9 interacts and co-functions with the NuRD (nucleosome remodeling and deacetylase) complex at enhancers; PAX9 depletion induces a primed-to-active enhancer transition increasing neural differentiation gene expression; pharmacological HDAC inhibition reverses PAX9/NuRD-mediated repression. Genome-wide CRISPR-Cas9 dropout screen, ChIP-seq, ATAC-seq, co-immunoprecipitation (PAX9-NuRD), HDAC inhibitor treatment, gene expression analysis Cancer research High 34341073
2004 Pax9 regulates region-specific epithelial differentiation in the tongue; Pax9-deficient mice lack normal filiform papilla polarity with altered Hoxc13 expression, have disturbed barrier formation, and show downregulation of 'hard' keratins (Krt1-5, Krt1-24, Krt2-16) with upregulation of 'soft' skin-specific keratins (Krt2-1, Krt2-17), indicating partial trans-differentiation towards skin-type epithelium. Knockout mouse, genome-wide expression profiling, in situ hybridization Mechanisms of development High 15454262
2002 Pax9 is required in thymic epithelial cells for normal thymopoiesis; in Pax9 null mice the thymic anlage fails to perform its normal caudo-ventral migration and remains as an ectopic structure in the larynx; the rudiment expresses Whn/Foxn1 and is colonized by T cell progenitors but is severely reduced in size from E14.5; TCRγ chain expression is lost while TCRβ is maintained. Knockout mouse analysis, immunostaining, in situ hybridization, RT-PCR for TCR chains European journal of immunology High 11932925

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities. Genes & development 636 9732271
1995 Characterization and developmental expression of Pax9, a paired-box-containing gene related to Pax1. Developmental biology 232 7649395
1999 Pax1 and Pax9 synergistically regulate vertebral column development. Development (Cambridge, England) 204 10556064
1993 Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9. Nature genetics 200 7981748
2001 Identification of a nonsense mutation in the PAX9 gene in molar oligodontia. European journal of human genetics : EJHG 134 11781684
2002 A novel mutation in human PAX9 causes molar oligodontia. Journal of dental research 125 11827258
2004 MSX1, PAX9, and TGFA contribute to tooth agenesis in humans. Journal of dental research 124 15329380
2011 Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes. American journal of medical genetics. Part A 117 21626677
2002 Embryonic submandibular gland morphogenesis: stage-specific protein localization of FGFs, BMPs, Pax6 and Pax9 in normal mice and abnormal SMG phenotypes in FgfR2-IIIc(+/Delta), BMP7(-/-) and Pax6(-/-) mice. Cells, tissues, organs 116 11731698
2002 Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia. Human genetics 115 11941488
2010 Genetic interactions between Pax9 and Msx1 regulate lip development and several stages of tooth morphogenesis. Developmental biology 114 20123092
2003 Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome. Development (Cambridge, England) 108 12490554
2006 Functional consequences of interactions between Pax9 and Msx1 genes in normal and abnormal tooth development. The Journal of biological chemistry 101 16651263
2003 Novel missense mutations and a 288-bp exonic insertion in PAX9 in families with autosomal dominant hypodontia. American journal of medical genetics. Part A 95 12605438
1996 Expression of avian Pax1 and Pax9 is intrinsically regulated in the pharyngeal endoderm, but depends on environmental influences in the paraxial mesoderm. Developmental biology 93 8812138
2000 Uncx4.1 is required for the formation of the pedicles and proximal ribs and acts upstream of Pax9. Development (Cambridge, England) 91 10804168
2003 A missense mutation in PAX9 in a family with distinct phenotype of oligodontia. European journal of human genetics : EJHG 87 14571272
2005 Novel mutation of the initiation codon of PAX9 causes oligodontia. Journal of dental research 85 15615874
2013 Pax9 regulates a molecular network involving Bmp4, Fgf10, Shh signaling and the Osr2 transcription factor to control palate morphogenesis. Development (Cambridge, England) 83 24173808
2005 Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development. Mechanisms of development 81 16169709
2003 Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. The Journal of biological chemistry 78 12657635
2005 Reduction of Pax9 gene dosage in an allelic series of mouse mutants causes hypodontia and oligodontia. Human molecular genetics 71 16236760
1998 Pax genes and organogenesis: Pax9 meets tooth development. European journal of oral sciences 71 9541201
2003 A novel missense mutation in the paired domain of PAX9 causes non-syndromic oligodontia. Human genetics 66 14689302
1996 Zebrafish Pax9 encodes two proteins with distinct C-terminal transactivating domains of different potency negatively regulated by adjacent N-terminal sequences. The Journal of biological chemistry 63 8900176
2006 Molecular characterization of a novel PAX9 missense mutation causing posterior tooth agenesis. European journal of human genetics : EJHG 61 16479262
2003 Novel mutation in the paired box sequence of PAX9 gene in a sporadic form of oligodontia. European journal of oral sciences 60 12786960
2017 Small-molecule Wnt agonists correct cleft palates in Pax9 mutant mice in utero. Development (Cambridge, England) 58 28893947
2002 Thymopoiesis requires Pax9 function in thymic epithelial cells. European journal of immunology 58 11932925
2006 New syndromic form of benign hereditary chorea is associated with a deletion of TITF-1 and PAX-9 contiguous genes. Movement disorders : official journal of the Movement Disorder Society 56 17044090
2017 Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice. Journal of dental research 55 28692808
2000 Pax1/Pax9-Related genes in an agnathan vertebrate, Lampetra japonica: expression pattern of LjPax9 implies sequential evolutionary events toward the gnathostome body plan. Developmental biology 55 10882524
2002 Progressive loss of PAX9 expression correlates with increasing malignancy of dysplastic and cancerous epithelium of the human oesophagus. The Journal of pathology 54 12115874
2017 A developmental transcriptomic analysis of Pax1 and Pax9 in embryonic intervertebral disc development. Biology open 51 28011632
1995 Differential expression of the chicken Pax-1 and Pax-9 gene: in situ hybridization and immunohistochemical analysis. Developmental dynamics : an official publication of the American Association of Anatomists 51 7647370
2005 PAX9 and TGFB3 are linked to susceptibility to nonsyndromic cleft lip with or without cleft palate in the Japanese: population-based and family-based candidate gene analyses. Journal of human genetics 50 16247549
2017 PAX9 gene mutations and tooth agenesis: A review. Clinical genetics 48 28155232
2005 Studies on Pax9-Msx1 protein interactions. Archives of oral biology 47 15721141
2014 G-quadruplex formation enhances splicing efficiency of PAX9 intron 1. Human genetics 46 25204874
2003 Identification of Cis-regulatory elements in the mouse Pax9/Nkx2-9 genomic region: implication for evolutionary conserved synteny. Genetics 46 14504231
2003 Functional analysis of a mutation in PAX9 associated with familial tooth agenesis in humans. The Journal of biological chemistry 46 14607846
1993 A new Pax gene, Pax-9, maps to mouse chromosome 12. Mammalian genome : official journal of the International Mammalian Genome Society 46 8358169
2006 A novel mutation in PAX9 causes familial form of molar oligodontia. European journal of human genetics : EJHG 45 16333316
2004 Pax9 is required for filiform papilla development and suppresses skin-specific differentiation of the mammalian tongue epithelium. Mechanisms of development 45 15454262
2009 Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer. Proceedings of the National Academy of Sciences of the United States of America 44 19279207
2009 Pathogenic mechanisms of tooth agenesis linked to paired domain mutations in human PAX9. Human molecular genetics 43 19429910
1999 De novo deletion (14)(q11.2q13) including PAX9: clinical and molecular findings. Journal of medical genetics 43 10204852
2017 Nine Novel PAX9 Mutations and a Distinct Tooth Agenesis Genotype-Phenotype. Journal of dental research 41 28910570
2010 PAX9 and MSX1 transcription factor genes in non-syndromic dental agenesis. Archives of oral biology 41 21111400
2008 Pbx1/Pbx2 govern axial skeletal development by controlling Polycomb and Hox in mesoderm and Pax1/Pax9 in sclerotome. Developmental biology 38 18691704
2011 Osr2 acts downstream of Pax9 and interacts with both Msx1 and Pax9 to pattern the tooth developmental field. Developmental biology 37 21420399
2017 A review on non-syndromic tooth agenesis associated with PAX9 mutations. The Japanese dental science review 36 29628999
2006 Exclusion of coding region mutations in MSX1, PAX9 and AXIN2 in eight patients with severe oligodontia phenotype. Orthodontics & craniofacial research 36 16918677
2006 Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development. Proceedings of the National Academy of Sciences of the United States of America 35 16585527
2017 PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium. The Journal of pathology 34 29055049
2005 Association between PAX-9 promoter polymorphisms and hypodontia in humans. Archives of oral biology 33 16137495
1999 Expression of the paired-box genes Pax-1 and Pax-9 in limb skeleton development. Developmental dynamics : an official publication of the American Association of Anatomists 33 10030590
2019 Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis. Development (Cambridge, England) 32 31444215
2015 Differentiation of Odontoblast-Like Cells From Mouse Induced Pluripotent Stem Cells by Pax9 and Bmp4 Transfection. Stem cells translational medicine 32 26136503
2011 Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family. Archives of oral biology 32 21530942
2010 Non-syndromic oligodontia with a novel mutation of PAX9. Journal of dental research 32 21098475
2007 A novel nonsense mutation in PAX9 is associated with marked variability in number of missing teeth. European journal of oral sciences 32 17697174
2007 Identification of a novel mutation in the PAX9 gene in a family affected by oligodontia and other dental anomalies. European journal of oral sciences 32 18028048
2003 Aberrant Pax1 and Pax9 expression in Jarcho-Levin syndrome: report of two Caucasian siblings and literature review. American journal of medical genetics. Part A 32 12833407
2014 Novel PAX9 mutations cause non-syndromic tooth agenesis. Journal of dental research 31 24436340
2008 Tooth dimensions in hypodontia with a known PAX9 mutation. Archives of oral biology 31 18653171
2008 Identification and functional analysis of two novel PAX9 mutations. Cells, tissues, organs 30 18701815
2007 A novel missense mutation in the paired domain of human PAX9 causes oligodontia. American journal of medical genetics. Part A 30 17910065
2014 The formation of endoderm-derived taste sensory organs requires a Pax9-dependent expansion of embryonic taste bud progenitor cells. PLoS genetics 29 25299669
2018 The Function and Regulatory Network of Pax9 Gene in Palate Development. Journal of dental research 28 30583699
2006 Temporal and spatial expression of Pax9 and Sonic hedgehog during development of normal mouse palates and cleft palates in TGF-beta3 null embryos. Archives of oral biology 26 17097601
2013 Characterization of pax1, pax9, and uncx sclerotomal genes during Xenopus laevis embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 24 23401059
2012 Novel PAX9 and COL1A2 missense mutations causing tooth agenesis and OI/DGI without skeletal abnormalities. PloS one 24 23227268
2008 Function of Pax1 and Pax9 in the sclerotome of medaka fish. Genesis (New York, N.Y. : 2000) 24 18395830
2023 Tooth agenesis patterns and variants in PAX9: A systematic review. The Japanese dental science review 23 37159578
2010 Mutations in the PAX9 gene in sporadic oligodontia. Orthodontics & craniofacial research 23 20618716
2008 PAX9 polymorphisms and susceptibility to sporadic tooth agenesis: a case-control study in southeast China. European journal of oral sciences 23 18353002
2008 Pax9 mediated cell survival in oral squamous carcinoma cell enhanced by c-myb. Cell biochemistry and function 23 18979497
2016 Effects of PAX9 and MSX1 gene variants to hypodontia, tooth size and the type of congenitally missing teeth. Cellular and molecular biology (Noisy-le-Grand, France) 21 28040065
2015 A novel initiation codon mutation of PAX9 in a family with oligodontia. Archives of oral biology 21 26571067
2013 SNPs and interaction analyses of IRF6, MSX1 and PAX9 genes in patients with non‑syndromic cleft lip with or without palate. Molecular medicine reports 21 23921572
2012 Novel missense mutations in PAX9 causing oligodontia. Archives of oral biology 21 22277187
2021 PAX9 Determines Epigenetic State Transition and Cell Fate in Cancer. Cancer research 20 34341073
2017 Anti-EDAR Agonist Antibody Therapy Resolves Palate Defects in Pax9-/- Mice. Journal of dental research 20 28813171
2012 Novel missense mutation in PAX9 gene associated with familial tooth agenesis. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 20 22747565
2022 PAX9 reactivation by inhibiting DNA methyltransferase triggers antitumor effect in oral squamous cell carcinoma. Biochimica et biophysica acta. Molecular basis of disease 19 35533906
2010 Mutational analysis of MSX1 and PAX9 genes in Portuguese families with maxillary lateral incisor agenesis. European journal of orthodontics 18 20660504
2005 [Novel mutations of PAX9 gene in Chinese patients with oligodontia]. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 18 16191360
2019 Familial oligodontia and regional odontodysplasia associated with a PAX9 initiation codon mutation. Clinical oral investigations 17 30809714
2019 Genotyping analysis of the Pax9 Gene in patients with maxillary canine impaction. F1000Research 17 31069070
2013 Novel PAX9 mutation associated with syndromic tooth agenesis. European journal of oral sciences 17 24028587
2020 Functional study of novel PAX9 variants: The paired domain and non-syndromic oligodontia. Oral diseases 16 33078491
2013 Mutational analysis of AXIN2, MSX1, and PAX9 in two Mexican oligodontia families. Genetics and molecular research : GMR 16 24222224
2012 Association between PAX9 single-nucleotide polymorphisms and nonsyndromic cleft lip with or without cleft palate. The Journal of craniofacial surgery 16 22976623
2011 A novel nonsense mutation in PAX9 is associated with sporadic hypodontia. Mutagenesis 16 22058014
2022 PAX9 in Cancer Development. International journal of molecular sciences 15 35628401
2020 Pax9's dual roles in modulating Wnt signaling during murine palatogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 15 32390226
2001 Comparative analysis of the genomic organization of Pax9 and its conserved physical association with Nkx2-9 in the human, mouse, and pufferfish genomes. Mammalian genome : official journal of the International Mammalian Genome Society 15 11252173
2011 Genetic basis of non syndromic hypodontia: a DNA investigation performed on three couples of monozygotic twins about PAX9 mutation. European journal of paediatric dentistry 14 21434731
2008 Association between the development of the body axis and the craniofacial skeleton studied by immunohistochemical analyses using collagen II, Pax9, Pax1, and Noggin antibodies. Spine 14 18594453