Affinage

TBX18

T-box transcription factor TBX18 · UniProt O95935

Length
607 aa
Mass
64.8 kDa
Annotated
2026-04-28
63 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBX18 is a T-box transcription factor that functions primarily as a transcriptional repressor to drive mesenchymal progenitor differentiation into specialized cell types across multiple organ systems, including sinoatrial node pacemaker myocardium, ureteral and aortic smooth muscle, otic fibrocytes, and epicardial derivatives. TBX18 homodimerizes and heterodimerizes with TBX15, binds T half-sites on DNA, and represses transcription in a Groucho-dependent manner, recruiting cofactors including ZMYM2 (CoREST complex), CBFB, CHD7, and IKZF2 while competing with activating T-box factors such as TBX5 for target promoters (PMID:17584735, PMID:30071041, PMID:34935912). Direct transcriptional targets include Cx43 (repressed, leading to electrical uncoupling in cardiomyocytes), Slug (promoting epicardial EMT), CHN1 (activated, elevating RhoA signaling), and immediate early genes EGR1/FOS/JUNB in aortic smooth muscle cells (PMID:21205823, PMID:23469079, PMID:37399907, PMID:41263385). Dominant-negative TBX18 mutations cause congenital anomalies of the kidney and urinary tract (CAKUT) in humans through impaired DNA binding and transcriptional repression (PMID:26235987).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 Medium

    Establishing where TBX18 is expressed — its restriction to proepicardium, epicardium, somite anterior halves, and urogenital mesenchyme — defined the developmental contexts in which it could function.

    Evidence In situ hybridization during mouse embryonic development

    PMID:11118889

    Open questions at the time
    • Expression pattern alone does not establish function
    • No protein-level validation
  2. 2004 High

    The first functional role was established: TBX18 maintains anterior-posterior somite compartmentalization, acting downstream of Delta/Notch signaling and Mesp2, resolving how somite polarity is imposed at the transcription factor level.

    Evidence Tbx18 knockout mice with posterior somite compartment expansion, ectopic expression, and genetic epistasis

    PMID:15155583

    Open questions at the time
    • Direct transcriptional targets in somites not identified
    • Molecular mechanism of compartment boundary maintenance unclear
  3. 2006 High

    TBX18 was shown to be required in two additional mesenchymal progenitor populations — cardiac sinus horn precursors and ureteral mesenchyme — establishing it as a broad regulator of mesenchymal-to-differentiated cell fate transitions.

    Evidence Tbx18 knockout mice showing failure of sinus horn formation from Nkx2-5-negative mesenchyme and failure of ureteral smooth muscle differentiation with hydroureter

    PMID:16511601 PMID:16709898

    Open questions at the time
    • Direct target genes mediating smooth muscle vs. fibrous fate decision unknown
    • Whether sinus horn and ureter roles share common transcriptional targets unclear
  4. 2007 High

    The molecular mechanism of TBX18 was defined: it homodimerizes, heterodimerizes with TBX15, binds T half-sites, represses transcription via Groucho, and competes with TBX5 for target promoters — resolving how a T-box factor can act as a repressor rather than activator.

    Evidence Luciferase reporters, protein-protein interaction assays, dimerization assays, T half-site binding, in vivo ectopic expression in somitic mesoderm

    PMID:17584735

    Open questions at the time
    • Genome-wide binding sites not mapped
    • Groucho interaction domain on TBX18 not precisely delineated
  5. 2008 High

    TBX18 was placed in the sinoatrial node developmental hierarchy: it drives mesenchymal progenitor differentiation into pacemaker myocardium upstream of TBX3, and is separately required for otic fibrocyte differentiation and hearing, broadening its role beyond the cardiovascular system.

    Evidence Genetic lineage tracing and explant assays for SAN; transgenic rescue and ABR measurements for inner ear; Tbx18 KO analysis; PAX3 co-IP and double-mutant analysis for somite role

    PMID:18353863 PMID:18644785 PMID:19096026

    Open questions at the time
    • How TBX18 activates Tbx3 expression mechanistically is unknown
    • Whether PAX3-TBX18 interaction is direct or bridged not fully resolved
  6. 2011 High

    A first direct transcriptional target in the heart was identified: TBX18 directly represses the Cx43 promoter, causing electrical uncoupling of cardiomyocytes — explaining how TBX18 imposes pacemaker-like properties by suppressing gap-junctional communication.

    Evidence Adenoviral overexpression in neonatal rat cardiomyocytes, promoter-reporter assay, dye transfer, calcium imaging, electrophysiology

    PMID:21205823

    Open questions at the time
    • Whether Cx43 repression is T-box-dependent or through cofactor recruitment not distinguished
    • Other direct target genes in pacemaker conversion not yet identified
  7. 2012 High

    TBX18 was shown to be sufficient for direct reprogramming of ventricular cardiomyocytes into functional pacemaker cells in vivo, demonstrating it as a master regulator of pacemaker identity capable of overriding the working myocardial program.

    Evidence Adenoviral gene transfer in guinea-pig hearts with patch-clamp electrophysiology, morphological analysis, and correction of bradycardia

    PMID:23242162

    Open questions at the time
    • Subsequent in vivo misexpression study found incomplete pacemaker gene induction in fetal chambers (PMID:27180262)
    • Long-term stability of reprogrammed pacemaker cells not established
  8. 2013 High

    The mechanism by which TBX18 controls epicardial EMT and vascular remodeling was delineated: TBX18 directly binds the Slug promoter to promote EMT, and represses smooth muscle differentiation via SRF/CArG box-dependent repression, positioning it as a gatekeeper of epicardial cell fate.

    Evidence ChIP and promoter assays for Slug binding, siRNA knockdown with TGFβ1 treatment, SRF/CArG reporter assays, Tbx18 KO vascular phenotype analysis

    PMID:23469079 PMID:23685333 PMID:24016759

    Open questions at the time
    • Whether Slug is the sole EMT mediator downstream of TBX18 not resolved
    • Relationship between CArG-dependent repression and Groucho-dependent repression unclear
  9. 2015 High

    Dominant-negative TBX18 mutations were identified as a cause of human CAKUT, establishing the disease relevance and demonstrating that dimerization with wild-type protein and impaired DNA binding underlie the dominant-negative mechanism.

    Evidence Whole exome sequencing of CAKUT patients, transcriptional repression assays, dimerization assays, protein stability and DNA-binding assays with mutant proteins

    PMID:26235987

    Open questions at the time
    • Penetrance and spectrum of TBX18 mutations in broader CAKUT cohorts not defined
    • Whether dominant-negative mechanism applies equally in cardiac and otic tissues unknown
  10. 2018 High

    An expanded cofactor network was mapped: unbiased proteomics identified CBFB, CHD7, IKZF2 as enhancers and NCOA5, SBNO2 as relievers of TBX18 repression, while TBX18 overexpression in pacemaker tissue induced HCN2 isoform switching to restore SAN function.

    Evidence Tandem affinity purification and LC-MS with functional validation; gene transfer in rat subsidiary atrial pacemaker tissue with electrophysiology and computational modeling

    PMID:30071041 PMID:30259525

    Open questions at the time
    • Which cofactors are relevant in which tissue context not determined
    • Whether HCN isoform switch is a direct or indirect TBX18 target unknown
  11. 2022 High

    The molecular basis of TBX18-mediated pacemaker reprogramming was comprehensively defined: proteome-wide remodeling involves upregulation of pacemaker ion channels, mechanosensitive channels, and EMT transcription factors, while TBX18 was shown to recruit the CoREST complex via direct interaction with ZMYM2.

    Evidence TMT proteomics and RNAseq of TBX18-transduced cardiomyocytes; CRISPR/Cas9 endogenous tagging with anti-FLAG AP-MS identifying ZMYM2, validated by multiple binding assays

    PMID:34935912 PMID:36006872

    Open questions at the time
    • Whether CoREST recruitment is required for pacemaker reprogramming not tested
    • Direct vs. indirect targets among the remodeled proteome not distinguished
  12. 2025 High

    TBX18 was established as essential for aortic smooth muscle homeostasis in both development and adulthood: ChIP-seq in human aortic SMCs revealed direct binding to immediate early genes, and adult conditional ablation synergized with Marfan mutation to cause lethal aortic dilation.

    Evidence Embryonic and adult conditional KO mice, ChIP-seq in primary human aortic SMCs, transcriptomic and translatomic analyses

    PMID:41263385

    Open questions at the time
    • Whether TBX18 loss contributes to sporadic human aortic disease not established
    • How TBX18 repression of immediate early genes maintains SMC quiescence mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the genome-wide direct target repertoire of TBX18 across its diverse tissue contexts, how cofactor switching (Groucho vs. CoREST vs. CBFB/CHD7) determines tissue-specific transcriptional outputs, and whether TBX18 acts as both repressor and activator at distinct loci or whether apparent activation (e.g., CHN1) is indirect.
  • No genome-wide binding data outside aortic SMCs
  • Mechanism of context-dependent switching between repression and activation undefined
  • Structural basis of TBX18 dimerization and cofactor selectivity not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 3
Partners
CBFBCHD7GATA4IKZF2PAX3SIX1TBX15ZMYM2
Complex memberships
CoREST complex (via ZMYM2)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 TBX18 is expressed during mouse development most prominently in the proepicardial organ and epicardium of the heart, as well as in cranial paraxial mesoderm, presomitic mesoderm, anterior somite half, genital ridge, and developing limb buds, establishing its tissue-specific expression pattern. Cloning and expression analysis (in situ hybridization) Mechanisms of development Medium 11118889
2004 TBX18 maintains the separation of anterior and posterior somite compartments: Tbx18-deficient mice show expansion of posterior-derived vertebral elements due to posterior cells invading the anterior somite half, and ectopic Tbx18 expression promotes anterior at the expense of posterior somite compartments. TBX18 acts downstream of Mesp2 and Delta/Notch signaling and functions as an antiapoptotic factor in the anterior lateral sclerotome. Tbx18 knockout mouse phenotypic analysis, ectopic expression experiments, genetic epistasis Genes & development High 15155583
2006 TBX18 is required for formation of the myocardial sinus horns at the venous pole of the heart from an Nkx2-5-negative mesenchymal precursor population: Tbx18-deficient mice fail to form sinus horns from pericardial mesenchyme and have defective caval veins. Tbx18 knockout mouse analysis, genetic lineage tracing, expression analysis Circulation research High 16709898
2006 TBX18 is required for development of ureteral mesenchyme: in Tbx18-/- mice, ureteral mesenchymal cells fail to condense and differentiate into smooth muscle but instead become fibrous and ligamentous tissue, resulting in hydroureter and hydronephrosis. TBX18 is expressed in undifferentiated mesenchymal cells surrounding the distal ureter stalk. Tbx18 knockout mouse phenotypic analysis, histology, expression analysis The Journal of clinical investigation High 16511601
2007 TBX18 and TBX15 homo- and heterodimerize, bind various combinations of T half-sites, and repress transcription in a Groucho-dependent manner. TBX18 interacts with GATA4 and NKX2-5 and competes with TBX5-mediated activation of the ANP (Natriuretic peptide precursor type a) promoter. Ectopic TBX18 down-regulates TBX6-activated Delta-like 1 expression in somitic mesoderm in vivo. Functional domains for nuclear localization, DNA binding, and transcriptional modulation were characterized. Luciferase reporter assays, protein-protein interaction assays, dimerization assays, T half-site binding assays, in vivo ectopic expression The Journal of biological chemistry High 17584735
2008 TBX18-expressing mesenchymal progenitors in the inflow tract region differentiate into pacemaker myocardium to form the sinoatrial node (SAN) head. Tbx18 is required to establish the large SAN head structure from mesenchymal precursors; Tbx18-deficient fetuses have only a very small but still functional tail piece. Tbx18 acts upstream of Tbx3, which subsequently imposes the pacemaker gene program on the SAN. Genetic lineage analysis, explant assays, Tbx18-knockout mouse analysis, genetic epistasis with Tbx3 Circulation research High 19096026
2008 Tbx18-expressing epicardial progenitors give rise to myocytes in the ventricular septum and atrial and ventricular walls, as well as cardiac fibroblasts and coronary smooth muscle cells, identifying a myocardial lineage derived from Tbx18 epicardial cells. Genetic lineage tracing (Tbx18-Cre mouse), immunostaining, histological analysis Nature Medium 18480752
2008 Differentiation of otic fibrocytes requires TBX18: Tbx18-deficient mice exhibit profound deafness and complete disruption of the endocochlear potential. Tbx18-mutant otic fibrocytes fail to generate the basal cell layer of stria vascularis by mesenchymal-epithelial transition, and lineage restriction between otic fibrocytes and otic capsule is severely affected. Transgenic rescue approach, auditory brainstem response measurements, histological analysis of inner ear, Tbx18-knockout mice Development (Cambridge, England) High 18353863
2008 TBX18 protein physically interacts with PAX3, and both are co-expressed in anterior presomitic mesoderm and early somites. Loss of Pax3 enhances vertebral defects in Tbx18 mutant mice, demonstrating cooperative function in maintaining anterior-posterior somite polarity and scapula blade development. Co-immunoprecipitation/protein interaction assays, genetic interaction analysis (double mutants), expression analysis The Journal of biological chemistry High 18644785
2009 TBX18 gene is itself expressed in myocardium, demonstrating that the Tbx18-Cre lineage tracing system used by Cai et al. does not allow conclusions of an epicardial origin of cardiomyocytes to be drawn, as Tbx18 expression in myocardium confounds the lineage tracing interpretation. Expression analysis (in situ hybridization, immunostaining) in embryonic mouse hearts Nature High 19369973
2010 SIX1 and TBX18 genetically interact to synergistically regulate ureteral smooth muscle cell (SMC) development: SIX1 is required for maintenance and differentiation of SM progenitors, and SIX1/TBX18 gene products form a protein complex in cultured cells and in the developing ureter. Two BOR patient SIX1 missense mutations reduced or abolished SIX1-TBX18 complex formation. Genetic interaction (double mutant analysis), co-immunoprecipitation in cultured cells and tissue, patient mutation analysis Development (Cambridge, England) High 20110314
2011 TBX18 directly represses the Cx43 (connexin43) promoter in cardiomyocytes, specifically downregulating Cx43 transcript and protein while leaving Cx45 and Cx40 unchanged. TBX18-mediated Cx43 suppression leads to electrical uncoupling of cardiomyocytes, slowed conduction velocity (>50% reduction), and asynchronous calcium oscillations, recapitulating a hallmark of the sinoatrial node. Adenoviral overexpression in neonatal rat cardiomyocytes, reporter-based promoter assay, Western blotting, dye transfer assays, calcium imaging, in vivo injection, electrophysiology The Journal of biological chemistry High 21205823
2012 TBX18 expression is sufficient to directly convert rodent ventricular cardiomyocytes to sinoatrial node (SAN)-like pacemaker cells in vitro and in vivo. Tbx18-transduced cardiomyocytes develop spontaneous electrical firing physiologically indistinguishable from SAN cells, acquire cardinal tapering morphology, and correct bradycardic disease phenotype in guinea-pig ventricle. In vivo adenoviral gene transfer in guinea-pig, in vitro cardiomyocyte transduction, electrophysiology (patch-clamp), morphological analysis, epigenetic profiling Nature biotechnology High 23242162
2012 A transcriptional activator version of TBX18 (TBX18VP16) causes premature smooth muscle cell differentiation of epicardial cells; this phenotype is reverted by inhibition of Notch and TGF-beta receptor signaling in explant cultures, indicating that TBX18 repressor activity prevents premature SMC differentiation by repressing TGF-beta receptor and Notch signaling in the epicardium. Transgenic mouse overexpression of TBX18VP16, epicardial explant cultures with pharmacological inhibitors Cardiovascular research Medium 22926762
2013 TBX18 and WT1 bi-directionally control epicardial EMT through regulation of Slug expression: TBX18 knockdown inhibits TGFbeta1-induced mesenchymal transition and decreases Slug expression, while WT1 knockdown induces EMT and increases Slug expression. Chromatin immunoprecipitation and promoter assays show TBX18 and WT1 directly bind to the Slug promoter region. siRNA knockdown, TGFbeta1 treatment, ChIP assay, luciferase promoter assay, migration assays, immunostaining PloS one High 23469079
2013 TBX18 possesses SRF/CArG box-dependent repressor activity capable of inhibiting progenitor cell differentiation into smooth muscle cells. Tbx18-deficient epicardial cells exhibit defective vascular plexus remodeling and altered expression of 79 genes associated with vascular development including sonic hedgehog signaling components, VEGF-A, angiopoietin-1, endoglin, and Wnt factors. Tbx18 knockout mouse analysis, PECAM-1 whole mount immunostaining, vascular cast analysis, gene expression profiling, reporter assays Developmental biology High 24016759
2013 TBX18 is exclusively required within the ureteric mesenchymal lineage to suppress a renal stromal fate: Tbx18-deficient ureteric mesenchymal cells adopt a stromal rather than ureteric smooth muscle fate. DiI labeling and tissue recombination experiments show the restriction of Tbx18 expression to prospective ureteric mesenchyme is due to loss of Tbx18 expression in cells out of range of signals from ureteric epithelium, and Tbx18-deficient cells do not respond to epithelial signals. Genetic lineage tracing, DiI labeling, tissue recombination experiments, Tbx18 knockout analysis Developmental biology High 23685333
2015 Dominant-negative TBX18 mutations cause human CAKUT by interference with TBX18 transcriptional repression activity. Mutant TBX18 proteins still dimerize with wild-type protein but have prolonged protein half-life and reduced transcriptional repression. The p.Lys163Glu substitution alters an amino acid critical for TBX18-DNA interaction, resulting in impaired TBX18-DNA binding. Whole exome sequencing, transcriptional repression assays, dimerization assays, protein stability assays, DNA-binding assays, mutagenesis American journal of human genetics High 26235987
2016 Misexpression of TBX18 in fetal mouse cardiac chambers does not induce a pacemaker-like gene signature (SAN gap junction and ion channel profile not ectopically induced), but partially inhibits the working myocardial gene program in atria and ventricles and strongly represses left atrial expression of Pitx2. Conditional misexpression using chamber-specific Cre driver lines (Myh6-Cre, Tagln-Cre) with Hprt(Tbx18) allele, molecular analysis of cardiac gene programs Journal of molecular and cellular cardiology High 27180262
2016 TBX18 is required for differentiation of periductal smooth muscle stromal cells in the prostate: Tbx18-deficient cells fail to condense into smooth muscle cells of periductal prostatic stroma and instead assume a hypertrophic myofibroblastic state, leading to disorganized epithelium. Genes regulating cell proliferation, smooth muscle differentiation, and inflammatory response are significantly dysregulated in mutant urogenital sinus. Tbx18 hypomorphic and conditional knockout mouse models, histological analysis, gene expression analysis of embryonic urogenital sinus PloS one High 27120339
2018 TBX18 overexpression in subsidiary atrial pacemaker tissue restores SAN function by inducing a switch in dominant HCN isoform, with significant upregulation of HCN2, leading to increased rate, improved heart rate stability, and restored isoprenaline response. Computer modeling confirmed HCN isoform-specific changes could account for observed beating rate changes. Gene overexpression in rat subsidiary atrial pacemaker tissue, electrophysiology, qRT-PCR, computer modeling The Journal of physiology High 30259525
2018 TBX18 binding partners identified by tandem purification and LC-MS include transcriptional cofactors (CBFB, GAR1, IKZF2, NCOA5, SBNO2, CHD7) and homeobox transcription factors. CBFB, CHD7 and IKZF2 enhanced TBX18 transcriptional repression, while NCOA5 and SBNO2 dose-dependently relieved it. All tested homeobox factors interacted with the T-box of TBX18 in pull-down assays. Tandem affinity purification, LC-MS, nuclear recruitment assays, GST pull-down, transcriptional repression assays PloS one High 30071041
2022 TBX18 reprograms ventricular cardiomyocytes into pacemaker cells by triggering vast proteome remodeling including increased expression of pacemaker ion channels (HCN4, CX45), mechanosensitive ion channels (Piezo1, Trpp2/PKD2, TrpM7), downregulation of metabolic pathways and ventricular ion channels, and extensive cytoskeletal/ECM remodeling with hallmarks of epithelial-to-mesenchymal transition (EMT). EMT-inducing transcription factors Snai1, Snai2, Twist1, Twist2, and Zeb2 are upregulated. Tandem mass tag proteomics, RNAseq, network diffusion mapping of transcriptional regulators Journal of proteome research High 36006872
2022 TBX18 protein binds to ZMYM2, a component of the CoREST transcriptional corepressor complex, identified by CRISPR/Cas9 endogenous tagging and anti-FLAG affinity purification followed by LC-MS. This interaction was confirmed by multiple binding assays. Tbx18 and Zmym2 are coexpressed in the mesenchymal compartment of the developing mouse ureter, and mutations in both genes are linked to CAKUT. CRISPR/Cas9 endogenous tagging, anti-FLAG affinity purification, LC-MS, multiple binding assays, expression analysis The Biochemical journal High 34935912
2022 MicroRNAs miR-1-3p and miR-1b suppress TBX18 protein expression from chemically modified mRNA (CMmRNA). Co-administration of antagomiRs against these miRs prolongs TBX18 expression in vitro and in vivo and is sufficient to generate electrical stimuli capable of pacing the heart in rats with atrioventricular block. CMmRNA transfection, small RNA sequencing, antagomiR co-administration, electrophysiology in AV-block rat model Cell reports. Medicine Medium 36543116
2023 TBX18 transcriptionally activates CHN1 by binding to its promoter region, thereby elevating RhoA activity. TBX18 knockdown reduces CHN1 transcription and RhoA activity, sensitizing esophageal squamous cell carcinoma cells to radiotherapy. Dual-luciferase reporter assay, ChIP assay, GST pull-down (for CHN1-RhoA), ectopic expression/knockdown, in vivo xenograft model Radiotherapy and oncology Medium 37399907
2025 TBX18 in smooth muscle cells (SMCs) is essential for normal aortic development and prevents adverse gene expression programs in adulthood. Embryonic conditional ablation of Tbx18 in SMCs causes severe aortic malformations. Adult ablation combined with Marfan mutation promotes aortic root dilation and lethality. ChIP-seq in primary human aortic SMCs reveals TBX18 directly binds to genes misexpressed in mutant aortae, including immediate early genes EGR1, FOS, and JUNB. Conditional knockout mouse models, ChIP-seq in primary human aortic SMCs, multiomics (transcriptomic and translatomic analyses), histological and quantitative imaging analyses Cardiovascular research High 41263385
2025 In atrial fibroblasts under rapid electrical stimulation, miR-1 modulates Cx43 expression through TBX18: miR-1 reduces TBX18 levels and increases Cx43 expression, while miR-1 antagomir suppresses TBX18 transcriptional activity on the Cx43 promoter. Luciferase reporter assays show miR-1 targets the TBX18 3'-UTR, and TBX18 siRNA upregulates Cx43, indicating TBX18 is a transcriptional repressor of Cx43 in this context. Luciferase reporter assays, miR-1 overexpression and antagomir treatment, siRNA knockdown, immunohistochemical staining Acta Cardiologica Sinica Medium 41608281

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 A myocardial lineage derives from Tbx18 epicardial cells. Nature 619 18480752
2008 Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3. Circulation research 245 19096026
2012 Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18. Nature biotechnology 244 23242162
2006 Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18. Circulation research 224 16709898
2009 Tbx18 and the fate of epicardial progenitors. Nature 217 19369973
2001 Cloning and expression analysis of the mouse T-box gene Tbx18. Mechanisms of development 183 11118889
2004 The T-box transcription factor Tbx18 maintains the separation of anterior and posterior somite compartments. Genes & development 142 15155583
2006 Tbx18 regulates the development of the ureteral mesenchyme. The Journal of clinical investigation 127 16511601
2013 Tbx18 regulates development of the epicardium and coronary vessels. Developmental biology 83 24016759
2007 Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors. The Journal of biological chemistry 82 17584735
2013 Tbx18 expression demarcates multipotent precursor populations in the developing urogenital system but is exclusively required within the ureteric mesenchymal lineage to suppress a renal stromal fate. Developmental biology 75 23685333
2015 Mutations in TBX18 Cause Dominant Urinary Tract Malformations via Transcriptional Dysregulation of Ureter Development. American journal of human genetics 67 26235987
2008 Deafness in mice lacking the T-box transcription factor Tbx18 in otic fibrocytes. Development (Cambridge, England) 59 18353863
2011 Transcriptional suppression of connexin43 by TBX18 undermines cell-cell electrical coupling in postnatal cardiomyocytes. The Journal of biological chemistry 57 21205823
2013 The transcription factors Tbx18 and Wt1 control the epicardial epithelial-mesenchymal transition through bi-directional regulation of Slug in murine primary epicardial cells. PloS one 56 23469079
1999 Identification, mapping, and phylogenomic analysis of four new human members of the T-box gene family: EOMES, TBX6, TBX18, and TBX19. Genomics 47 9888994
2002 Cloning of zebrafish T-box genes tbx15 and tbx18 and their expression during embryonic development. Mechanisms of development 46 12175500
2010 SIX1 acts synergistically with TBX18 in mediating ureteral smooth muscle formation. Development (Cambridge, England) 44 20110314
2016 Efficient Differentiation of TBX18+/WT1+ Epicardial-Like Cells from Human Pluripotent Stem Cells Using Small Molecular Compounds. Stem cells and development 40 27927069
2012 Tbx18 targets dermal condensates for labeling, isolation, and gene ablation during embryonic hair follicle formation. The Journal of investigative dermatology 39 22992803
2004 Analysis of TBX18 expression in chick embryos. Development genes and evolution 38 15257458
2012 Tbx18 function in epicardial development. Cardiovascular research 34 22926762
2008 T-box protein Tbx18 interacts with the paired box protein Pax3 in the development of the paraxial mesoderm. The Journal of biological chemistry 31 18644785
2018 TBX18 transcription factor overexpression in human-induced pluripotent stem cells increases their differentiation into pacemaker-like cells. Journal of cellular physiology 29 30078203
2011 Developmental patterns and characteristics of epicardial cell markers Tbx18 and Wt1 in murine embryonic heart. Journal of biomedical science 29 21871065
2004 Tbx18 and boundary formation in chick somite and wing development. Developmental biology 28 15063182
2014 Tbx18 is essential for normal development of vasculature network and glomerular mesangium in the mammalian kidney. Developmental biology 25 24727670
2018 TBX18 overexpression enhances pacemaker function in a rat subsidiary atrial pacemaker model of sick sinus syndrome. The Journal of physiology 22 30259525
2016 TBX18 gene induces adipose-derived stem cells to differentiate into pacemaker-like cells in the myocardial microenvironment. International journal of molecular medicine 20 27632938
2019 Engineered Cardiac Pacemaker Nodes Created by TBX18 Gene Transfer Overcome Source-Sink Mismatch. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 31763140
2016 Hypoxia induced the differentiation of Tbx18-positive epicardial cells to CoSMCs. Scientific reports 18 27456656
2016 Misexpression of Tbx18 in cardiac chambers of fetal mice interferes with chamber-specific developmental programs but does not induce a pacemaker-like gene signature. Journal of molecular and cellular cardiology 16 27180262
2010 Tbx18 and Tbx15 null-like phenotypes in mouse embryos expressing Tbx6 in somitic and lateral plate mesoderm. Developmental biology 14 20832395
2019 Bone morphogenetic protein 4 promotes the differentiation of Tbx18-positive epicardial progenitor cells to pacemaker-like cells. Experimental and therapeutic medicine 13 30906456
2018 Proteomic analysis identifies transcriptional cofactors and homeobox transcription factors as TBX18 binding proteins. PloS one 11 30071041
2017 Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells. International journal of molecular medicine 11 29207072
2019 Genetically Modified Porcine Mesenchymal Stem Cells by Lentiviral Tbx18 Create a Biological Pacemaker. Stem cells international 10 31814832
2018 Comparison of mouse brown and white adipose‑derived stem cell differentiation into pacemaker‑like cells induced by TBX18 transduction. Molecular medicine reports 10 29568953
2022 MicroRNA-dependent suppression of biological pacemaker activity induced by TBX18. Cell reports. Medicine 9 36543116
2021 Tbx18 promoted the conversion of human-induced pluripotent stem cell-derived cardiomyocytes into sinoatrial node-like pacemaker cells. Cell biology international 9 34882885
2017 Tbx18-dependent differentiation of brown adipose tissue-derived stem cells toward cardiac pacemaker cells. Molecular and cellular biochemistry 9 28382491
2016 Tbx18 Regulates the Differentiation of Periductal Smooth Muscle Stroma and the Maintenance of Epithelial Integrity in the Prostate. PloS one 9 27120339
2013 Novel and functional variants within the TBX18 gene promoter in ventricular septal defects. Molecular and cellular biochemistry 8 23749171
2022 Tbx18 Orchestrates Cytostructural Transdifferentiation of Cardiomyocytes to Pacemaker Cells by Recruiting the Epithelial-Mesenchymal Transition Program. Journal of proteome research 7 36006872
2019 Transcription Factor TBX18 Reprograms Vascular Smooth Muscle Cells of Ascending Aorta to Pacemaker-Like Cells. DNA and cell biology 7 31633376
2016 Lack of Genetic Interaction between Tbx18 and Tbx2/Tbx20 in Mouse Epicardial Development. PloS one 7 27253890
2022 Proteomic analysis identifies ZMYM2 as endogenous binding partner of TBX18 protein in 293 and A549 cells. The Biochemical journal 6 34935912
2017 Tbx18-positive cells differentiated from murine ES cells serve as proepicardial progenitors to give rise to vascular smooth muscle cells and fibroblasts. Biomedical research (Tokyo, Japan) 6 28794400
2018 Transcription factor Tbx18 induces the differentiation of c-kit+ canine mesenchymal stem cells (cMSCs) into SAN-like pacemaker cells in a co-culture model in vitro. American journal of translational research 5 30210689
2014 A distant downstream enhancer directs essential expression of Tbx18 in urogenital tissues. Developmental biology 5 24854998
2003 Allelic imbalance at intragenic markers of Tbx18 is a hallmark of murine osteosarcoma. Carcinogenesis 5 12663494
2019 [Role of over-expression of TBX3 and TBX18 in the enrichment and differentiation of human induced pluripotent stem cells into sinoatrial node-like cells]. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery 3 30983202
2018 In vitro study of the effects of reprogramming neonatal rat fibroblasts transfected with TBX18 on spontaneous beating in neonatal rat cardiomyocytes. Molecular medicine reports 3 30365101
2024 Single-cell RNA sequencing reveals the transcriptional heterogeneity of Tbx18-positive cardiac cells during heart development. Functional & integrative genomics 2 38265516
2021 Tbx18-positive cells-derived myofibroblasts contribute to renal interstitial fibrosis via transforming growth factor-β signaling. Experimental cell research 2 34118250
2018 An extended regulatory landscape drives Tbx18 activity in a variety of prostate-associated cell lineages. Developmental biology 2 30594504
2025 Biological pacemaker induced by focal cardiac transduction with AAV-TBX18. Molecular therapy : the journal of the American Society of Gene Therapy 1 41108077
2025 Transcription regulation by TBX18 in smooth muscle cells is essential for normal aortic development and homeostasis. Cardiovascular research 1 41263385
2023 TBX18 knockdown sensitizes esophageal squamous cell carcinoma to radiotherapy by blocking the CHN1/RhoA axis. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 1 37399907
2022 Epicardium-Derived Tbx18+ CDCs Transplantation Improve Heart Function in Infarcted Mice. Frontiers in cardiovascular medicine 1 35141286
2026 Exosomal MicroRNA-1 Regulate Cx43 Expression via Tbx18 in Culture Atrial Fibroblasts under Rapid Electrical Stimulation. Acta Cardiologica Sinica 0 41608281
2022 Generation of a human embryonic stem cell line (WAe009-A-78) carrying homozygous TBX18 knockout. Stem cell research 0 35533514
2016 Sonic hedgehog, TBX18, and TSHZ3 proteins involved in pyeloureteral motility development are overexpressed in ureteropelvic junction obstruction. An immunohistochemical, histopathological, and clinical comparative study. Saudi medical journal 0 27381532