Affinage

TBX1

T-box transcription factor TBX1 · UniProt O43435

Length
398 aa
Mass
43.1 kDa
Annotated
2026-04-28
100 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBX1 is a T-box transcription factor that serves as the principal dosage-sensitive regulator of pharyngeal apparatus development, controlling cardiac outflow tract morphogenesis, thymus and parathyroid organogenesis, craniofacial patterning, and inner ear development. TBX1 functions primarily in pharyngeal endoderm and second heart field mesoderm, where it directly activates target genes including Fgf8, Fgf10, Wnt5a, Vegfr3, and Gbx2 through T-box binding element occupancy, recruiting chromatin remodeling (BAF/Baf60a) and histone-modifying (Setd7, MOZ) complexes to promote H3K4 monomethylation and H3K9 acetylation at target loci (PMID:22438823, PMID:22921202). TBX1 maintains cardiac progenitor proliferation while suppressing premature differentiation by binding and inhibiting serum response factor (SRF), and exerts a transcription-independent function by binding Smad1 to antagonize BMP signaling (PMID:19745164, PMID:19557177). Loss-of-function mutations in TBX1 cause DiGeorge/velocardiofacial syndrome in both mouse models and human patients lacking the 22q11.2 deletion (PMID:11242110, PMID:14585638).

Mechanistic history

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

    Establishing TBX1 as the critical gene for DiGeorge syndrome resolved a long-standing question about which gene within the 22q11.2 deletion interval drives the multi-organ phenotype.

    Evidence Targeted Tbx1 null mutation in mice recapitulating the full DGS spectrum; Shh-dependent Tbx1 expression in pharyngeal endoderm/mesoderm demonstrated in mouse and chick

    PMID:11242110 PMID:11412027

    Open questions at the time
    • Upstream cis-regulatory elements controlling Tbx1 expression not yet defined
    • Mechanism of dosage sensitivity not explained
  2. 2003 High

    Identification of TBX1 point mutations in non-deleted DGS patients and demonstration of cell-autonomous function in pharyngeal mesendoderm confirmed TBX1 as a direct human disease gene and defined its tissue of action.

    Evidence Human mutation screening in non-deleted DGS patients; cell transplantation in zebrafish van gogh mutant

    PMID:12952905 PMID:14585638

    Open questions at the time
    • Genotype-phenotype correlations for different TBX1 mutations not established
    • Penetrance modifiers not identified
  3. 2004 High

    Conditional and compound genetic experiments established that Tbx1 acts through Fgf8 in pharyngeal endoderm to pattern arch arteries and controls branchiomeric myogenesis and inner ear neurogenesis, revealing its multi-tissue selector-like functions.

    Evidence Tbx1-Cre conditional Fgf8 deletion; Tbx1 KO showing failed Myf5/MyoD activation; Tbx1 KO inner ear analysis

    PMID:12223416 PMID:14975726 PMID:15084464 PMID:15385444

    Open questions at the time
    • Direct transcriptional targets not yet identified by ChIP
    • Whether Tbx1 directly binds Fgf8 regulatory elements unknown
  4. 2005 High

    Identification of a disease-disrupted nuclear localization signal and retinoic acid-mediated repression of Tbx1 defined both a loss-of-function mechanism in DGS patients and a key upstream regulatory input.

    Evidence NLS mutagenesis linked to 1223delC mutation; RA-dependent Tbx1 repression in quail embryos and P19 cells

    PMID:15703190 PMID:15736167

    Open questions at the time
    • RA-responsive cis-regulatory element at Tbx1 locus not identified
    • Other post-translational regulatory mechanisms unexplored
  5. 2006 High

    Tissue-specific deletion in pharyngeal endoderm recapitulated the full null phenotype, genetic interaction with Crkl revealed RA metabolism as a modifier, and Tbx1 haploinsufficiency caused behavioral deficits, broadening the syndrome phenotype beyond structural malformations.

    Evidence Foxg1-Cre conditional KO; Crkl/Tbx1 compound heterozygotes with RA rescue; behavioral PPI testing of Tbx1+/- mice

    PMID:16399080 PMID:16452092 PMID:16684884

    Open questions at the time
    • Neural circuit basis of PPI deficit not mapped
    • Whether pharyngeal endoderm requirement reflects signaling to neural crest or mesoderm not resolved
  6. 2009 High

    Discovery of Tbx1's transcription-independent function — binding Smad1 to suppress BMP signaling — and identification of downstream effectors Gbx2/Slit-Robo for neural crest guidance and Fgf8 for thyroid development revealed dual mechanistic modes and expanded the target gene network.

    Evidence Co-IP of Tbx1-Smad1 with separation-of-function mutations and transgenic rescue; Gbx2 conditional mutants; Tbx1-Cre Fgf8 conditional KO with genetic rescue for thyroid

    PMID:19389367 PMID:19557177 PMID:19700621

    Open questions at the time
    • Structural basis of Tbx1-Smad1 interaction unknown
    • Full repertoire of transcription-independent functions not mapped
  7. 2009 High

    Tbx1 was shown to maintain cardiac progenitor proliferation and suppress differentiation by binding SRF, and genetic interaction with CHD7 revealed shared pharyngeal ectoderm requirements.

    Evidence Clonal analysis with Tbx1 gain/loss-of-function and Tbx1-SRF Co-IP; Chd7/Tbx1 compound heterozygotes

    PMID:19745164 PMID:19855134

    Open questions at the time
    • Whether Tbx1-SRF interaction is direct or through a complex not resolved
    • Full set of SRF target genes affected by Tbx1 not defined
  8. 2012 High

    ChIP-based identification of direct Tbx1 binding at Wnt5a and Fgf10 loci, plus demonstration that Tbx1 recruits BAF/Baf60a and Setd7 to catalyze H3K4me1, established the chromatin-level mechanism of Tbx1 transcriptional activation. MOZ was independently shown to maintain Tbx1 expression through H3K9 acetylation.

    Evidence ChIP for Tbx1 at Wnt5a and Fgf10; Co-IP of Tbx1-Baf60a and Tbx1-Setd7; MOZ ChIP at Tbx1 locus with genetic rescue

    PMID:22438823 PMID:22921202 PMID:23093675

    Open questions at the time
    • Genome-wide map of Tbx1-bound enhancers not generated
    • Structural basis of Tbx1-Baf60a interaction not resolved
  9. 2014 High

    Tbx1 was found to regulate epithelial polarity, basal filopodia dynamics, and cell survival in second heart field and pharyngeal mesoderm, and to segregate outflow from inflow progenitor populations, linking transcription factor function to morphogenetic cell behaviors.

    Evidence Live imaging and aPKCζ pharmacological phenocopy in SHF; transcriptomics and dye-labeling of OFT/inflow progenitors; TUNEL assays in conditional KO

    PMID:24705356 PMID:25190705 PMID:25371366

    Open questions at the time
    • Direct transcriptional targets mediating polarity and filopodia effects not identified
    • Whether aPKCζ regulation is direct or indirect unclear
  10. 2019 High

    Tbx1 was shown to non-cell-autonomously maintain ECM-integrin-focal adhesion signaling in the SHF and to genetically interact with Pax9 in pharyngeal endoderm, revealing extracellular matrix and co-transcription factor mechanisms.

    Evidence Conditional KO with focal adhesion/migration assays and mosaic analysis; Tbx1/Pax9 compound heterozygotes with Pax9Cre conditional allele

    PMID:31180501 PMID:31444215

    Open questions at the time
    • Specific ECM components regulated by Tbx1 not identified
    • Direct versus indirect Tbx1-Pax9 interaction not tested
  11. 2021 High

    Single-cell genomics revealed that Tbx1 marks a multilineage-primed cardiopharyngeal progenitor population and restricts ectopic gene expression through chromatin accessibility changes, providing a genome-wide view of its role as a lineage gatekeeper.

    Evidence scRNA-seq and ATAC-seq in Tbx1 loss-of-function mouse embryos with lineage tracing

    PMID:34789765

    Open questions at the time
    • Whether Tbx1 directly binds at ATAC-seq differential sites not tested
    • Epigenetic memory mechanisms downstream of Tbx1 unknown
  12. 2023 High

    Beyond development, Tbx1 was discovered to drive an immunosuppressive program in lymphatic endothelial cells after myocardial infarction and to non-autonomously control cardiac neural crest cell transitions through BMP/MAPK signaling balance.

    Evidence LEC-specific Tbx1 conditional KO with immune cell phenotyping post-MI; scRNA-seq of NCCs from Tbx1 null embryos with signaling pathway and Tbx2/Tbx3 genetic validation

    PMID:36941249 PMID:37625409

    Open questions at the time
    • Upstream signals activating Tbx1 in adult LECs after injury unknown
    • Whether the post-MI immunomodulatory role is conserved in humans not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A genome-wide map of direct Tbx1 binding sites in relevant tissues, the structural basis of Tbx1 interactions with chromatin remodelers and signaling effectors, and the mechanisms underlying dosage sensitivity remain unresolved.
  • No genome-wide ChIP-seq for Tbx1 in pharyngeal tissues reported
  • Structural basis of Tbx1-Baf60a and Tbx1-Smad1 interactions not determined
  • Molecular basis of haploinsufficiency/dosage sensitivity not mechanistically explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 10 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 2 R-HSA-168256 Immune System 1
Partners
ASH2LCHD7CRKLPITX2SETD7SMAD1SMARCD1SRF

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Tbx1 null mice display the full spectrum of DiGeorge/velocardiofacial syndrome features (cardiac outflow tract abnormalities, thymus and parathyroid hypoplasia, abnormal facial structures, cleft palate), and Tbx1 heterozygotes show cardiac outflow tract anomalies, establishing Tbx1 as the key gene for DGS/VCFS in a loss-of-function mouse model. Targeted null mutation in mice (loss-of-function genetics) with phenotypic analysis Nature genetics High 11242110
2003 Point mutations in TBX1 (missense and frameshift) are found in humans with DiGeorge/velocardiofacial syndrome phenotypes lacking the 22q11.2 deletion, establishing TBX1 as a major genetic determinant of the syndrome. Genetic sequencing of TBX1 coding sequence in non-deleted patients with del22q11.2 syndrome phenotype Lancet High 14585638
2001 Tbx1 expression in pharyngeal endoderm and mesodermal core is dependent on Sonic hedgehog (Shh) signaling; Shh is sufficient to induce Tbx1 expression when misexpressed in chick embryos, placing Tbx1 downstream of Shh in pharyngeal arch development. Mouse Shh mutant analysis, chick misexpression experiments, in situ hybridization Developmental biology High 11412027
2002 Tbx1 genetically interacts with Fgf8 in development of the fourth pharyngeal arch artery; Fgf8 expression is abolished in pharyngeal endoderm of Tbx1-/- mutants, and double heterozygous Tbx1+/-;Fgf8+/- mice show significantly higher penetrance of aortic arch artery defects than either single heterozygote. Compound heterozygous mouse genetics (epistasis), in situ hybridization Development High 12223416
2004 Tbx1 is required for branchiomeric myogenesis: in Tbx1 null mice, myogenic determination genes Myf5 and MyoD fail to be normally activated in pharyngeal mesoderm, and unspecified precursor cells expressing Capsulin and MyoR persist in the mandibular arch. Loss-of-function mouse genetics with gene expression analysis (in situ hybridization, immunohistochemistry) Human molecular genetics High 15385444
2004 Fgf8 functions downstream of Tbx1: tissue-specific inactivation of Fgf8 in Tbx1-expressing cells (using Tbx1-Cre mice) causes DiGeorge-like cardiovascular defects, and vascular smooth muscle differentiation in great vessels is disrupted, supporting a model where Tbx1 induces Fgf8 expression in pharyngeal endoderm. Conditional knockout using Tbx1-Cre driver; fate mapping of Tbx1-expressing precursors Developmental biology High 14975726
2004 Tbx1 suppresses neurogenin 1-mediated neural fate determination in the otocyst epithelium and is required for induction/patterning of sensory organ genes (Otx1, Bmp4); loss of Tbx1 causes dysregulation of neural competence and duplication of the VIIIth ganglion rudiment. Loss-of-function mouse genetics with in situ hybridization and histological analysis of inner ear Development High 15084464
2005 A novel nuclear localization signal (NLS) at the C-terminus of Tbx1 is deleted by the disease-associated 1223delC mutation, explaining the mechanism of loss-of-function in these DiGeorge syndrome patients. Mutagenesis, subcellular localization assays, functional analysis of NLS Human molecular genetics High 15703190
2005 Retinoic acid (RA) down-regulates Tbx1 expression in a dose-dependent manner in both avian embryos and P19 cells; this effect is independent of the Shh/Foxa2 regulatory pathway and requires de novo protein synthesis for maximal repression. RA bead implantation in quail embryos, real-time PCR in RA-treated P19 cells, vitamin A-deficient quail model Developmental dynamics High 15736167
2006 Compound heterozygosity of Tbx1 and Crkl (both 22q11 genes) causes a striking increase in DiGeorge syndrome-like phenotype penetrance and expressivity; Tbx1 and Crkl have dose-dependent functions in pharyngeal segmentation and local regulation of retinoic acid metabolism. Reduction of RA production partially rescues the pharyngeal phenotype in Crkl+/-;Tbx1+/- embryos. Compound heterozygous mouse genetics, genetic rescue experiments, RA pathway analysis Developmental cell High 16399080
2006 Inactivation of Tbx1 specifically in the pharyngeal endoderm (using Foxg1-Cre) recapitulates the full Tbx1 homozygous null phenotype including failed pharyngeal pouch outgrowth, thymus aplasia, and cardiac outflow tract malformations, demonstrating that Tbx1 in the pharyngeal endoderm is required for patterning and development of the pharyngeal apparatus. Conditional knockout using Cre/loxP system (Foxg1-Cre driver) with phenotypic analysis Development High 16452092
2006 Tbx1 haploinsufficiency causes prepulse inhibition (PPI) deficits in mice, a schizophrenia endophenotype, establishing Tbx1 as a contributor to behavioral/psychiatric phenotypes in 22q11DS independent of its role in physical malformations. Behavioral testing of single-gene Tbx1 heterozygous mouse mutants; deletion mapping using overlapping deletions PNAS High 16684884
2006 Tbx1 controls the population, proliferation, and cell fate determination of otic epithelial cells cell-autonomously; loss of Tbx1 switches the fate of some Tbx1-dependent cells from non-neurogenic to neurogenic via activation of the Delta-Notch pathway. Cochlear morphogenesis additionally requires mesodermal Tbx1 expression (cell non-autonomous). Timed cell fate mapping, conditional ablation, BrdU proliferation assays, in situ hybridization Developmental biology High 17074316
2007 A fate map of Tbx1-expressing cells (using Tbx1-Cre knock-in) shows they constitute a mesodermal population surrounding the primitive pharynx that populates most of the outflow tract (but not the anterior portion), and gives rise to both myocardial and endocardial cell types, suggesting a common origin. Tbx1-Cre knock-in lineage tracing with reporter and 3D image reconstruction Genesis High 17610275
2008 Tbx1 controls regional outflow tract identity and coronary artery patterning; loss of Tbx1 reduces and malpositions a subdomain of myocardium at the base of the pulmonary trunk, associated with anomalous coronary artery patterning. Semaphorin3c is identified as a Tbx1-dependent gene expressed in subpulmonary myocardium. Genetic crosses with transgenic markers, genetic lineage tracing, in situ hybridization Circulation research High 18583714
2008 Tbx1 is expressed in multipotent cardiac progenitor cells (CPCs) of the second heart field; in these cells Tbx1 stimulates proliferation, and loss of Tbx1 causes premature differentiation while gain prevents differentiation. Tbx1 binds serum response factor (SRF) and negatively regulates its levels, identifying a mechanism by which Tbx1 inhibits muscle differentiation. Clonal analysis, loss- and gain-of-function in vivo and in vitro, co-immunoprecipitation (Tbx1-SRF interaction), immunostaining Circulation research High 19745164
2008 Tbx1 downstream target genes in the second heart field (SHF) include Isl1, Fgf genes, and myocardial differentiation genes; pan-mesodermal Tbx1 ablation shows cell-autonomous roles in regulating these genes. Tbx1 positively regulates SHF cell proliferation and negatively regulates differentiation. Gene expression profiling of Tbx1-/- pharyngeal region, conditional deletion (pan-mesodermal), gain-of-function transgenic mice Developmental biology High 18328475
2009 Tbx1 regulates Vegfr3 transcription by directly binding to an enhancer element in the Vegfr3 gene in endothelial cells (ECs); conditional deletion of Tbx1 in ECs causes widespread lymphangiogenesis defects and perinatal death, demonstrating a role in lymphatic vessel growth and maintenance. ChIP (Tbx1 binding to Vegfr3 enhancer), conditional EC-specific knockout, cellular and molecular analyses Journal of Cell Biology High 20439995
2009 Tbx1 binds Smad1 directly and suppresses BMP4/Smad1 signaling by interfering with Smad1-Smad4 complex formation; a Tbx1 mutation that abolishes transactivation does not prevent Smad1 binding, while a disease-associated TBX1 mutation prevents TBX1-SMAD1 interaction but not transactivation, demonstrating a transactivation-independent function. Co-immunoprecipitation (Tbx1-Smad1), mutagenesis of Tbx1 (transactivation and Smad1-binding mutations), luciferase reporter assays, transgenic mouse rescue PLoS ONE High 19557177
2009 CHD7 and Tbx1 genetically interact in the pharyngeal ectoderm: biallelic expression of both Chd7 and Tbx1 in pharyngeal ectoderm is required for normal fourth pharyngeal arch artery development, and Tbx1+/-;Chd7+/- double heterozygotes show synergistic defects. Compound heterozygous mouse genetics, neural crest-specific conditional rescue, phenotypic analysis Journal of Clinical Investigation High 19855134
2009 Tbx1 controls pharyngeal neural crest cell (cNCC) migration by regulating Gbx2 expression in pharyngeal surface ectoderm; Gbx2 downstream of Tbx1 triggers directional cues to cNCCs via the Slit/Robo signaling pathway, required for caudal pharyngeal arch artery formation. Mouse genetics (Tbx1 and Gbx2 conditional mutants), cNCC migration analysis, gene expression studies Development High 19700621
2009 Tbx1 regulates early thyroid primordium size through expression in adjacent mesoderm, acting upstream of Fgf8 in mesodermal cells; conditional ablation of Fgf8 in Tbx1-expressing cells recapitulates the early thyroid size defect, and Fgf8 cDNA expression in the Tbx1 domain rescues the thyroid size defect in Tbx1 mutants. Conditional knockout of Fgf8 using Tbx1-Cre, genetic rescue experiment, in situ hybridization Developmental biology High 19389367
2010 Ash2l (a core component of a histone methyltransferase complex) physically interacts with Tbx1 in both yeast and mammalian cells and acts as a transcriptional co-activator in reporter assays, suggesting Tbx1 functions are mediated in part through interaction with a histone methyltransferase complex. Yeast two-hybrid screen, co-immunoprecipitation, luciferase reporter assay, Ash2l knockout mouse Experimental biology and medicine Medium 20463296
2010 Canonical Wnt/beta-catenin signaling negatively regulates Tbx1 expression; mesenchymal inactivation of beta-catenin in mice causes DGS-like phenotypes, and ectopic Wnt activation worsens phenotypes in Fgf8+/- or Tbx1+/- backgrounds, placing Wnt-beta-catenin upstream of the Tbx1-Fgf8 signaling pathway. Conditional mouse knockouts (beta-catenin), compound heterozygous genetics, Wnt gain-of-function, in situ hybridization Development High 20215350
2011 A genetic pathway Tbx1→Six1/Eya1→Fgf8 controls cardiovascular and craniofacial morphogenesis; Six1 and Eya1 are direct upstream activators of Fgf8 and genetically interact with Tbx1 in mice. Mouse genetics (compound mutants), ChIP, luciferase reporter assays, in situ hybridization Journal of Clinical Investigation High 21364285
2011 Ripply3 suppresses Tbx1 transcriptional activation activity in luciferase assays and represses Tbx1-induced expression of Pax9; Ripply3-deficient mice exhibit upregulated Pax9 and abnormal pharyngeal apparatus development, establishing Ripply3 as a repressor of Tbx1. Luciferase reporter assay, Ripply3 knockout mouse, in situ hybridization Development Medium 21177346
2011 Tbx1 deficiency affects Tbx2 and Tbx3 expression in neural crest cells and pharyngeal mesoderm; Tbx2 and Tbx3 function redundantly upstream of Tbx1 and Hedgehog ligand expression in pharyngeal endoderm, revealing a Tbx gene regulatory network governing pharyngeal and outflow tract development. Mouse genetics (conditional and compound mutants), expression analysis, 3D reconstruction Human molecular genetics Medium 22116936
2012 Tbx1 is a transcriptional activator of Wnt5a in the second heart field; Tbx1 occupies T-box binding elements within the Wnt5a gene, interacts with the Baf60a/Smarcd1 subunit of the BAF chromatin remodeling complex and with Setd7 histone H3K4 monomethyltransferase, enhances Baf60a occupation at Wnt5a, and promotes H3K4 monomethylation. Baf60a is required for Tbx1-driven target gene regulation. ChIP (Tbx1 binding to Wnt5a), Co-IP (Tbx1-Baf60a, Tbx1-Setd7), compound mutant mouse genetics, ChIP for histone modification PLoS genetics High 22438823
2012 MOZ histone acetyltransferase complex occupies the Tbx1 locus and promotes Tbx1 expression and histone H3 lysine 9 acetylation; MOZ mutation phenocopies DiGeorge syndrome, and a Tbx1 transgene rescues the heart phenotype in Moz mutants. ChIP (MOZ complex at Tbx1 locus), Moz knockout mouse, histone acetylation analysis, genetic rescue with Tbx1 transgene Developmental cell High 22921202
2012 Tbx1 directly activates Vegfr3 transcription (shown previously) and additionally regulates DLL4 in brain endothelial cells; loss of Tbx1 causes brain vessel hyperplasia and hyperbranching via the DLL4/Notch1-VEGFR3 axis. A Notch1 agonist partially rescues TBX1 knockdown-induced microtubule hyperbranching in EC cultures. EC-specific conditional Tbx1 knockout, 3D matrigel EC culture, Notch1 agonist rescue, loss-of-function genetics Human molecular genetics High 23945394
2012 Tbx1 directly controls Fgf10 expression in the anterior second heart field through a 1.7-kb regulatory element in the first intron of Fgf10; this element responds to Tbx1, Nkx2-5, and Islet1, with Nkx2-5 repressing and Isl1 activating Fgf10 in differentiated myocardium. Transgenic reporter analysis, ChIP (Islet1 binding in vivo), loss- and gain-of-function mouse genetics PNAS High 23093675
2010 Tbx1 regulates progenitor cell proliferation in dental epithelium by inhibiting Pitx2 transcriptional activity; Tbx1 physically interacts with the PITX2 C-terminus and represses PITX2 activation of p21, LEF-1, and Pitx2c promoters. Tbx1 null MEFs show increased Pitx2a and Pitx2c expression. Co-immunoprecipitation (Tbx1-Pitx2), ChIP (Pitx2 on p21 promoter), luciferase reporter assay, Tbx1/Pitx2 compound heterozygous mouse genetics Developmental biology High 20816801
2012 Tbx1 genetically interacts with Smad7 (an inhibitory TGF-β/BMP signaling component) in great vessel remodeling; Tbx1 acts upstream of Smad7, and concurrent haploinsufficiency of both genes impairs vascular smooth muscle cell coverage and fibronectin deposition of the fourth arch artery. Conditional Smad7 reconstitution with Tbx1-Cre shows the interaction is cell autonomous. Compound heterozygous mouse genetics, conditional reconstitution with Tbx1-Cre, vascular smooth muscle phenotypic analysis Circulation research High 23011393
2014 Tbx1 regulates epithelial polarity and dynamic basal filopodia in second heart field (SHF) cells; loss of Tbx1 causes increased cell circularity, reduced basolateral membrane domain, and impaired filopodial activity associated with elevated aPKCζ levels. Activation of aPKCζ in embryo culture phenocopies proliferative defects and ectopic differentiation seen in Tbx1 null SHF. Immunofluorescence, live imaging, embryo culture, aPKCζ pharmacological activation Development High 25371366
2014 Tbx1 is required in the second heart field (SHF) for both outflow tract and venous pole (inflow) morphogenesis; Tbx1 null embryos fail to segregate OFT progenitor cells from the posterior SHF progenitor pool and show abnormal dorsal pericardial wall expansion and atrioventricular septal defects. Transcriptome analysis, genetic tracing, fluorescent dye-labeling in mouse embryos Circulation research High 25190705
2014 In zebrafish, Tbx1 functions in the mesoderm to promote pharyngeal pouch morphogenesis through wnt11r and fgf8a expression; compound loss of wnt11r and fgf8a phenocopies tbx1 mutant pouch defects, and mesoderm-specific restoration of Wnt11r and Fgf8a rescues tbx1 mutant pouches. Fgf8a acts as a Wnt11r-dependent guidance cue for migrating pouch cells. Zebrafish mutant/transgenic rescue experiments, time-lapse imaging, compound loss-of-function Development High 25142463
2014 Tbx1 is required autonomously in pharyngeal core mesoderm for cell survival and myogenic fate between E9.5 and E10.5; loss of Tbx1 causes apoptosis of core mesoderm cells and reduction of branchiomeric muscles. Tbx1 acts upstream of key myogenic bHLH transcription factors in pharyngeal arch mesoderm. Lineage tracing (Mesp1-Cre, T-Cre), conditional KO, TUNEL apoptosis assays, gene expression profiling Human molecular genetics High 24705356
2019 Tbx1 is required to maintain integrity of extracellular matrix (ECM)-integrin-focal adhesion (FA) signaling in the second heart field in a non-cell autonomous manner; loss of TBX1 impairs cell migration and focal adhesions in cultured cells. Interfering with ECM-integrin-FA axis during E8.5–E9.5 in mouse embryos causes outflow tract dysmorphogenesis. Mouse conditional knockout, cultured cell loss-of-function, focal adhesion and migration assays, mosaic analysis Human molecular genetics High 31180501
2019 Tbx1 and Pax9 genetically interact in the pharyngeal endoderm; Pax9-deficient mice have cardiovascular malformations similar to Tbx1 mutants, and Tbx1/Pax9 double heterozygotes show significantly increased interrupted aortic arch. A Pax9Cre allele establishes that the Tbx1-Pax9 interaction occurs in pharyngeal endoderm. Pax9 knockout mouse, compound heterozygous genetics, Pax9Cre conditional allele, transcriptome analysis Development High 31444215
2021 Single-cell RNA-sequencing identifies a Tbx1-marked multilineage primed population in cardiopharyngeal mesoderm with bipotent properties to form cardiac and branchiomeric muscle cells; Tbx1 regulates maturation of these progenitors and restricts ectopic non-mesodermal gene expression partly through altering chromatin accessibility. Single-cell RNA-sequencing, ATAC-seq (chromatin accessibility), genetic lineage tracing, Tbx1 loss-of-function mouse Nature communications High 34789765
2023 Tbx1 in lymphatic endothelial cells (LECs) drives an immunosuppressive program after myocardial infarction; Tbx1-activated LECs penetrate the infarcted area and function as immune hubs that increase tolerogenic dendritic cells and regulatory T cells through Ccl21 and Icam1, inhibiting autoreactive CD8+ T cells and promoting reparative macrophage expansion. Tbx1 conditional knockout in LECs, single-cell analysis, gene expression studies, immune cell phenotyping Immunity High 37625409
2023 Loss of Tbx1 in mouse embryos non-autonomously disrupts three dynamic transitions of cardiac neural crest cells (CNCCs) from pharyngeal NCCs expressing Tbx2/Tbx3 through differentiated CNCCs; Tbx1 loss causes upregulation of BMP signaling and reduced MAPK signaling in CNCCs, leading to failed smooth muscle differentiation and aortic arch artery defects. Single-cell RNA-sequencing of NCCs from Tbx1 null and control embryos, cell-cell communication analysis, inactivation of Tbx2/Tbx3 in CNCCs Nature communications High 36941249
2011 Tbx1 protein and mRNA are expressed in postnatal brain regions retaining neurogenesis capacity and in proliferating neural progenitor cells; in hippocampal culture cells, Tbx1 levels are higher during proliferation than differentiation, suggesting a role in regulating neural progenitor cell biology. Immunohistochemistry, in situ hybridization in mouse brain, hippocampal cell culture with stage-specific analysis Human molecular genetics Medium 21908517
2003 In zebrafish, tbx1 (van gogh/vgo) acts cell autonomously in the pharyngeal mesendoderm and influences the development of neural crest-derived cartilages secondarily; regulatory interactions exist between vgo/tbx1 and edn1 and hand2 in pharyngeal arch development. Cell transplantation experiments in zebrafish, genetic analysis of van gogh mutant Development High 12952905

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nature genetics 802 11242110
2020 Dsuite - Fast D-statistics and related admixture evidence from VCF files. Molecular ecology resources 631 33012121
2003 Role of TBX1 in human del22q11.2 syndrome. Lancet (London, England) 604 14585638
1996 Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. Developmental dynamics : an official publication of the American Association of Anatomists 531 8853987
2006 Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proceedings of the National Academy of Sciences of the United States of America 237 16684884
2002 A genetic link between Tbx1 and fibroblast growth factor signaling. Development (Cambridge, England) 233 12223416
2001 Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development. Developmental biology 221 11412027
2004 The del22q11.2 candidate gene Tbx1 regulates branchiomeric myogenesis. Human molecular genetics 197 15385444
2022 A spectrum of free software tools for processing the VCF variant call format: vcflib, bio-vcf, cyvcf2, hts-nim and slivar. PLoS computational biology 188 35639788
2004 Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage. Human molecular genetics 182 15190012
2003 The zebrafish van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans. Development (Cambridge, England) 179 12952905
2006 Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Developmental cell 162 16399080
2004 Suppression of neural fate and control of inner ear morphogenesis by Tbx1. Development (Cambridge, England) 134 15084464
2005 Transcription, apoptosis and p53: catch-22. Trends in genetics : TIG 127 15734577
2006 Inactivation of Tbx1 in the pharyngeal endoderm results in 22q11DS malformations. Development (Cambridge, England) 121 16452092
2008 The del22q11.2 candidate gene Tbx1 controls regional outflow tract identity and coronary artery patterning. Circulation research 120 18583714
2009 Tbx1 regulates proliferation and differentiation of multipotent heart progenitors. Circulation research 118 19745164
2009 Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. The Journal of clinical investigation 118 19855134
2011 A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. The Journal of clinical investigation 112 21364285
2004 Cre-mediated excision of Fgf8 in the Tbx1 expression domain reveals a critical role for Fgf8 in cardiovascular development in the mouse. Developmental biology 111 14975726
2009 Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm. Development (Cambridge, England) 110 19700621
2008 Identification of downstream genetic pathways of Tbx1 in the second heart field. Developmental biology 109 18328475
2018 A catch-22: Interleukin-22 and cancer. European journal of immunology 95 29178520
2010 22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development. Pediatric cardiology 95 20054531
2012 Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium. Proceedings of the National Academy of Sciences of the United States of America 93 23093675
2005 Dissecting contiguous gene defects: TBX1. Current opinion in genetics & development 93 15917203
2014 Tbx1 coordinates addition of posterior second heart field progenitor cells to the arterial and venous poles of the heart. Circulation research 91 25190705
2012 Transcriptional control in cardiac progenitors: Tbx1 interacts with the BAF chromatin remodeling complex and regulates Wnt5a. PLoS genetics 91 22438823
2005 Retinoic acid down-regulates Tbx1 expression in vivo and in vitro. Developmental dynamics : an official publication of the American Association of Anatomists 89 15736167
2007 A fate map of Tbx1 expressing cells reveals heterogeneity in the second cardiac field. Genesis (New York, N.Y. : 2000) 84 17610275
2012 MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Developmental cell 83 22921202
2011 Tbx1: identification of a 22q11.2 gene as a risk factor for autism spectrum disorder in a mouse model. Human molecular genetics 72 21908517
2009 Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner. PloS one 71 19557177
2010 Ash2l interacts with Tbx1 and is required during early embryogenesis. Experimental biology and medicine (Maywood, N.J.) 67 20463296
2007 Tbx1 regulation of myogenic differentiation in the limb and cranial mesoderm. Developmental dynamics : an official publication of the American Association of Anatomists 66 17117436
2010 Tbx1 regulates Vegfr3 and is required for lymphatic vessel development. The Journal of cell biology 64 20439995
2013 NK4 antagonizes Tbx1/10 to promote cardiac versus pharyngeal muscle fate in the ascidian second heart field. PLoS biology 62 24311985
1997 The murine homologue of HIRA, a DiGeorge syndrome candidate gene, is expressed in embryonic structures affected in human CATCH22 patients. Human molecular genetics 62 9063745
2011 Identification of a Tbx1/Tbx2/Tbx3 genetic pathway governing pharyngeal and arterial pole morphogenesis. Human molecular genetics 61 22116936
2005 Identification of a novel nuclear localization signal in Tbx1 that is deleted in DiGeorge syndrome patients harboring the 1223delC mutation. Human molecular genetics 59 15703190
2014 TBX1 regulates epithelial polarity and dynamic basal filopodia in the second heart field. Development (Cambridge, England) 58 25371366
2005 Tbx1 is required for proper neural crest migration and to stabilize spatial patterns during middle and inner ear development. Mechanisms of development 58 15652707
2010 Systematic survey of variants in TBX1 in non-syndromic tetralogy of Fallot identifies a novel 57 base pair deletion that reduces transcriptional activity but finds no evidence for association with common variants. Heart (British Cardiac Society) 57 20937753
2016 Tbx1: Transcriptional and Developmental Functions. Current topics in developmental biology 54 28057265
2007 Mutations in TBX1 genocopy the 22q11.2 deletion and duplication syndromes: a new susceptibility factor for mental retardation. European journal of human genetics : EJHG 53 17377518
2012 Phenotypic variability of atypical 22q11.2 deletions not including TBX1. American journal of medical genetics. Part A 51 22893440
2012 The 22q11 deletion: DiGeorge and velocardiofacial syndromes and the role of TBX1. Wiley interdisciplinary reviews. Developmental biology 51 23799583
2013 Tbx1 regulates brain vascularization. Human molecular genetics 50 23945394
2011 Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients. Human mutation 50 21796729
2010 Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome. Developmental biology 50 20122914
2012 Tbx1 regulates oral epithelial adhesion and palatal development. Human molecular genetics 49 22371266
2011 Her9 represses neurogenic fate downstream of Tbx1 and retinoic acid signaling in the inner ear. Development (Cambridge, England) 48 21205785
2006 Tbx1 regulates population, proliferation and cell fate determination of otic epithelial cells. Developmental biology 48 17074316
2006 The 22q11 deletion syndrome candidate gene Tbx1 determines thyroid size and positioning. Human molecular genetics 48 17164259
2014 TBX1 mutation identified by exome sequencing in a Japanese family with 22q11.2 deletion syndrome-like craniofacial features and hypocalcemia. PloS one 47 24637876
2011 Ripply3, a Tbx1 repressor, is required for development of the pharyngeal apparatus and its derivatives in mice. Development (Cambridge, England) 47 21177346
2023 Lymphatic endothelial transcription factor Tbx1 promotes an immunosuppressive microenvironment to facilitate post-myocardial infarction repair. Immunity 46 37625409
2014 Tbx1 controls the morphogenesis of pharyngeal pouch epithelia through mesodermal Wnt11r and Fgf8a. Development (Cambridge, England) 43 25142463
2009 Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors. Developmental biology 43 19233155
1996 A transcription map in the CATCH22 critical region: identification, mapping, and ordering of four novel transcripts expressed in heart. Genomics 43 8786095
2021 Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm. Nature communications 42 34789765
2013 Understanding the role of Tbx1 as a candidate gene for 22q11.2 deletion syndrome. Current allergy and asthma reports 42 23996541
2012 Org-1, the Drosophila ortholog of Tbx1, is a direct activator of known identity genes during muscle specification. Development (Cambridge, England) 42 22318630
2008 Cooperative function of Tbx1 and Brn4 in the periotic mesenchyme is necessary for cochlea formation. Journal of the Association for Research in Otolaryngology : JARO 42 18231833
2008 Properties of branchiomeric and somite-derived muscle development in Tbx1 mutant embryos. Developmental dynamics : an official publication of the American Association of Anatomists 42 18816853
2006 Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests functional redundancy. Human molecular genetics 42 17000704
2008 A regulatory relationship between Tbx1 and FGF signaling during tooth morphogenesis and ameloblast lineage determination. Developmental biology 41 18572158
2007 Visualization of outflow tract development in the absence of Tbx1 using an FgF10 enhancer trap transgene. Developmental dynamics : an official publication of the American Association of Anatomists 40 17238155
2019 TBX1 Functions as a Tumor Suppressor in Thyroid Cancer Through Inhibiting the Activities of the PI3K/AKT and MAPK/ERK Pathways. Thyroid : official journal of the American Thyroid Association 39 30543152
2010 Tbx1 is necessary for palatal elongation and elevation. Mechanisms of development 38 20214979
2011 Tbx1, subpulmonary myocardium and conotruncal congenital heart defects. Birth defects research. Part A, Clinical and molecular teratology 37 21591244
2010 Canonical Wnt signaling modulates Tbx1, Eya1, and Six1 expression, restricting neurogenesis in the otic vesicle. Developmental dynamics : an official publication of the American Association of Anatomists 36 20503367
2012 Tbx1 genetically interacts with the transforming growth factor-β/bone morphogenetic protein inhibitor Smad7 during great vessel remodeling. Circulation research 35 23011393
2010 Tbx1 regulates progenitor cell proliferation in the dental epithelium by modulating Pitx2 activation of p21. Developmental biology 34 20816801
2018 Tbx1 regulates inherited metabolic and myogenic abilities of progenitor cells derived from slow- and fast-type muscle. Cell death and differentiation 33 30154444
2013 DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart looping and differentiation. PloS one 33 23533583
2010 Beta-catenin deficiency causes DiGeorge syndrome-like phenotypes through regulation of Tbx1. Development (Cambridge, England) 33 20215350
2009 Gain of function of Tbx1 affects pharyngeal and heart development in the mouse. Genesis (New York, N.Y. : 2000) 33 19253341
2009 Early thyroid development requires a Tbx1-Fgf8 pathway. Developmental biology 33 19389367
2002 Embryonic expression of Tbx1, a DiGeorge syndrome candidate gene, in the lamprey Lampetra fluviatilis. Gene expression patterns : GEP 33 12617845
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 A Novel TBX1 Loss-of-Function Mutation Associated with Congenital Heart Disease. Pediatric cardiology 31 25860641
2005 Eya1 acts upstream of Tbx1, Neurogenin 1, NeuroD and the neurotrophins BDNF and NT-3 during inner ear development. Mechanisms of development 31 15817220
2014 Tbx1 is required autonomously for cell survival and fate in the pharyngeal core mesoderm to form the muscles of mastication. Human molecular genetics 29 24705356
2014 Roles of retinoic acid and Tbx1/10 in pharyngeal segmentation: amphioxus and the ancestral chordate condition. EvoDevo 29 25664163
2010 The embryonic genes Dkk3, Hoxd8, Hoxd9 and Tbx1 identify muscle types in a diet-independent and fiber-type unrelated way. BMC genomics 28 20230627
2006 Developmental expression patterns of Tbx1, Tbx2, Tbx5, and Tbx20 in Xenopus tropicalis. Developmental dynamics : an official publication of the American Association of Anatomists 28 16477648
2023 Single-cell transcriptomics uncovers a non-autonomous Tbx1-dependent genetic program controlling cardiac neural crest cell development. Nature communications 27 36941249
2021 Tbx1, a gene encoded in 22q11.2 copy number variant, is a link between alterations in fimbria myelination and cognitive speed in mice. Molecular psychiatry 27 34737458
2019 Tbx1 regulates extracellular matrix-cell interactions in the second heart field. Human molecular genetics 27 31180501
2016 Rewiring of an ancestral Tbx1/10-Ebf-Mrf network for pharyngeal muscle specification in distinct embryonic lineages. Development (Cambridge, England) 27 27802138
2014 Endoderm-specific deletion of Tbx1 reveals an FGF-independent role for Tbx1 in pharyngeal apparatus morphogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 27 24812002
2014 Loss of Tbx1 induces bone phenotypes similar to cleidocranial dysplasia. Human molecular genetics 27 25209980
2006 TBX1, a DiGeorge syndrome candidate gene, is inhibited by retinoic acid. The International journal of developmental biology 27 16323078
2009 Chordin is a modifier of tbx1 for the craniofacial malformations of 22q11 deletion syndrome phenotypes in mouse. PLoS genetics 26 19247433
2010 Paraxial T-box genes, Tbx6 and Tbx1, are required for cranial chondrogenesis and myogenesis. Developmental biology 25 20692252
2017 BrowseVCF: a web-based application and workflow to quickly prioritize disease-causative variants in VCF files. Briefings in bioinformatics 24 27373737
2016 Coronary stem development in wild-type and Tbx1 null mouse hearts. Developmental dynamics : an official publication of the American Association of Anatomists 24 26708418
2014 Ectopic TBX1 suppresses thymic epithelial cell differentiation and proliferation during thymus organogenesis. Development (Cambridge, England) 23 25053428
2008 Retinoic acid down-regulates Tbx1 expression and induces abnormal differentiation of tongue muscles in fetal mice. Developmental dynamics : an official publication of the American Association of Anatomists 23 18816858