Affinage

TBX1

T-box transcription factor TBX1 · UniProt O43435

Length
398 aa
Mass
43.1 kDa
Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBX1 is a T-box transcription factor that orchestrates development of the pharyngeal apparatus and cardiovascular system by controlling progenitor cell proliferation, fate specification, and differentiation across multiple germ layers, and it is the haploinsufficient gene underlying the cardiovascular and pharyngeal features of the DiGeorge/22q11 deletion syndrome (PMID:11242049, PMID:16684884). It binds T-box DNA elements as a dimer (PMID:11111039) and acts as a context-dependent transcriptional regulator, directly activating Fgf8, Fgf10, and Vegfr3 enhancers in vivo (PMID:15469978, PMID:23093675, PMID:20439995) while negatively modulating Mef2c (PMID:22367967). In the second heart field TBX1 marks multipotent cardiopharyngeal progenitors and a bipotent multilineage-primed progenitor population, sustaining their proliferation and restricting premature differentiation, in part by binding SRF and by shaping chromatin accessibility (PMID:19745164, PMID:18328475, PMID:34789765). Beyond its transcriptional role, TBX1 functions non-transcriptionally by physically binding SMAD1 to suppress BMP/SMAD signaling and by interacting with PITX2 to repress its activity, distinctions resolvable with separation-of-function disease mutations (PMID:19557177, PMID:20816801, PMID:25556186). TBX1 lies within an upstream regulatory network—induced by Shh through tissue-specific Fox factors and a defined cis-element, repressed by retinoic acid, and activated epigenetically by the MOZ histone acetyltransferase complex via H3K9 acetylation (PMID:11412027, PMID:12533514, PMID:15736167, PMID:22921202)—and it acts upstream of effector pathways including Cyp26-mediated RA catabolism, Gbx2/Slit-Robo guidance of cardiac neural crest, Notch/Hes1, Semaphorin3c, and ECM-integrin-focal adhesion signaling to coordinate outflow tract, aortic arch artery, thymus, parathyroid, inner ear, branchiomeric muscle, and lymphatic vascular morphogenesis (PMID:17047027, PMID:19700621, PMID:20122914, PMID:18583714, PMID:31180501). In endothelium TBX1 controls angiogenesis and lymphangiogenesis through the DLL4/Notch1-VEGFR3 axis (PMID:20439995, PMID:23945394), and in lymphatic endothelial cells it drives an immunosuppressive program that promotes post-myocardial-infarction repair (PMID:37625409).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    Established which gene in the 22q11/DiGeorge interval is dosage-critical, answering whether a single gene accounts for the cardiovascular phenotype.

    Evidence Targeted heterozygous/homozygous deletion plus PAC transgenic rescue in mouse

    PMID:11242049

    Open questions at the time
    • Does not define the molecular mechanism by which TBX1 dosage controls arch artery growth
    • Cell-type responsible for the defect not yet resolved
  2. 2001 High

    Placed Tbx1 downstream of Shh, defining the upstream inductive signal driving its pharyngeal expression.

    Evidence In situ hybridization in Shh-null mice and Shh misexpression in chick

    PMID:11412027

    Open questions at the time
    • Direct vs indirect transcriptional link to Shh not resolved
    • Intermediary transcription factors not identified at this stage
  3. 2000 Medium

    Characterized the basic biochemistry of TBX1 DNA binding, showing it binds T-box palindromes as a dimer without intrinsic strong activation/repression in the assay used.

    Evidence In vitro DNA binding and transcriptional reporter assays

    PMID:11111039

    Open questions at the time
    • Reporter context did not reveal activator function later shown in vivo
    • No endogenous target context tested
  4. 2003 High

    Identified the cis-regulatory logic of Tbx1, showing Fox factors and Shh converge on a single essential enhancer.

    Evidence Enhancer reporter assays, transgenic mice, Fox binding/ChIP, Shh loss-of-function

    PMID:12533514 PMID:16444712

    Open questions at the time
    • Combinatorial inputs into the enhancer in different tissues not fully mapped
  5. 2002 High

    Distinguished cell-autonomous (pharyngeal growth) from non-autonomous (arch artery remodeling) functions, framing TBX1 as a tissue-instructive factor.

    Evidence Tbx1-lacZ reporter allele and phenotype/expression analysis in null mice; later six-Cre tissue-specific deletion

    PMID:11971873 PMID:16284121

    Open questions at the time
    • Identity of the secreted/relayed signals from epithelia to arch arteries not defined here
  6. 2002 High

    Connected TBX1 to FGF signaling genetically, identifying Fgf8 as dependent on Tbx1 and a sensitized double-heterozygote interaction.

    Evidence In situ hybridization and Tbx1;Fgf8 genetic intercross in mouse

    PMID:12223416 PMID:15175244 PMID:15469978 PMID:23093675

    Open questions at the time
    • Whether all FGF regulation is direct vs relayed varies by ligand and tissue
  7. 2005 High

    Defined the retinoic acid arm of TBX1 regulation, showing RA represses Tbx1 and that TBX1 in turn controls RA-degrading Cyp26 enzymes.

    Evidence Vitamin A-deficient quail, RA beads in chick, P19 cells; Cyp26 expression analysis and pharmacological inhibition

    PMID:15736167 PMID:16399080 PMID:17047027

    Open questions at the time
    • Direct vs indirect TBX1 regulation of Cyp26 genes not biochemically resolved
  8. 2006 High

    Mapped tissue-of-action across mesoderm, endoderm, and ectoderm, showing mesodermal Tbx1 is necessary and sufficient and that distinct lineages drive distinct derivatives.

    Evidence Mesoderm-, endoderm-, and ectoderm-specific Cre deletion and transgenic rescue in mouse

    PMID:16141220 PMID:16452092 PMID:16914493 PMID:19700621

    Open questions at the time
    • Molecular relays mediating non-autonomous effects only partly identified (e.g., Gbx2/Slit-Robo)
  9. 2009 High

    Revealed TBX1's progenitor-control mechanism, showing it sustains second-heart-field proliferation and blocks differentiation through binding SRF.

    Evidence Clonal analysis, in vivo/in vitro loss- and gain-of-function, Co-IP of Tbx1-SRF

    PMID:18328475 PMID:19745164 PMID:25371366 PMID:34789765

    Open questions at the time
    • Stoichiometry and structural basis of TBX1-SRF interaction unresolved
    • How chromatin remodeling integrates with SRF binding not defined
  10. 2009 High

    Established a transcription-independent function of TBX1, showing it binds SMAD1 to suppress BMP signaling, separable from its DNA-binding activity.

    Evidence Co-IP, separation-of-function transactivation mutants, transgenic gain-of-function and Smad1 rescue

    PMID:19557177 PMID:23011393 PMID:36941249

    Open questions at the time
    • Structural basis of TBX1-SMAD1 interaction not defined
    • Balance between transcriptional and non-transcriptional roles in vivo not quantified
  11. 2010 High

    Defined TBX1 as a direct transcriptional partner/antagonist of other factors, activating with NKX2.5/PITX2 enhancers and repressing PITX2 via direct binding.

    Evidence In vitro binding, ChIP, luciferase assays, conditional KO and double-heterozygote genetics, Co-IP

    PMID:16556915 PMID:20816801 PMID:25556186

    Open questions at the time
    • Switch between TBX1 activation vs repression of PITX2 by context not mechanistically resolved
  12. 2010 High

    Identified TBX1's direct endothelial role in (lymph)angiogenesis through Vegfr3 enhancer activation and the DLL4/Notch1-VEGFR3 axis.

    Evidence Enhancer binding assays, endothelial-specific conditional KO, 3D culture, Notch1 agonist rescue

    PMID:20439995 PMID:23945394

    Open questions at the time
    • Direct vs indirect regulation of DLL4 not biochemically established
  13. 2012 High

    Showed TBX1 expression is epigenetically activated, with the MOZ HAT complex occupying the locus and depositing H3K9 acetylation.

    Evidence ChIP for MOZ at Tbx1, MOZ KO/heterozygote genetics, Tbx1 transgenic rescue; plus Ash2l/Ripply3 cofactor studies

    PMID:20463296 PMID:21177346 PMID:22921202

    Open questions at the time
    • How MOZ recruitment to the Tbx1 locus is targeted not defined
  14. 2014 High

    Expanded TBX1's morphogenetic role to cell polarity, filopodial dynamics, and progenitor deployment to both cardiac poles.

    Evidence Live imaging, embryo culture, aPKCζ activation phenocopy; genetic tracing and dye labeling

    PMID:25190705 PMID:25371366

    Open questions at the time
    • Link between TBX1 transcriptional targets and aPKCζ/polarity machinery unresolved
  15. 2019 High

    Connected TBX1 to ECM-integrin-focal adhesion signaling as a non-autonomous determinant of outflow tract morphogenesis.

    Evidence Mouse embryo and cultured cell loss-of-function, mosaic analysis, pharmacological interference

    PMID:31180501

    Open questions at the time
    • Direct ECM/integrin gene targets of TBX1 not enumerated
  16. 2023 High

    Resolved single-cell signaling dynamics, showing TBX1 loss non-autonomously dysregulates BMP and MAPK communication to neural crest, and revealed a distinct LEC immunosuppressive role post-MI.

    Evidence scRNA-seq of Tbx1-null embryos and LEC-specific conditional KO with cell-cell communication analysis

    PMID:36941249 PMID:37625409

    Open questions at the time
    • Direct TBX1 targets driving the communication changes not pinpointed
    • Adult vs developmental mechanisms of LEC TBX1 not unified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TBX1 mechanistically switches between transcriptional activation, repression, and non-transcriptional cofactor sequestration in a tissue- and partner-specific manner remains unresolved.
  • No structural model integrating DNA binding, SRF/SMAD1/PITX2 interactions
  • Genome-wide direct target catalog across tissues incomplete
  • Quantitative contribution of transcriptional vs non-transcriptional activity to phenotypes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3
Partners
ASH2LNKX2-5PITX2RIPPLY3SMAD1SRF

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Tbx1 haploinsufficiency is sufficient to cause aortic arch defects (fourth pharyngeal arch artery defects) in mice in a gene dosage-dependent manner; homozygous mutation severely disrupts the pharyngeal arch artery system, establishing Tbx1 as the haploinsufficient gene within the DiGeorge chromosomal region. Chromosome engineering (targeted heterozygous and homozygous deletion), P1 artificial chromosome transgenesis, genetic rescue in mouse Nature High 11242049
2001 Tbx1 expression in pharyngeal arch development is regulated downstream of Sonic hedgehog (Shh) signaling; Shh is sufficient to induce Tbx1 expression when misexpressed in chick embryos, and Tbx1 expression is lost in Shh-null mouse embryos. In situ hybridization in Shh-null mice, Shh misexpression in chick embryos Developmental biology High 11412027
2002 Tbx1 deficiency causes a cell-autonomous function in the growth of the pharyngeal apparatus and a cell non-autonomous function in growth and remodeling of pharyngeal arch arteries, as shown by Tbx1-lacZ reporter allele analysis. Tbx1-lacZ reporter allele, phenotype/expression comparison in Tbx1 null mice Human molecular genetics Medium 11971873
2002 Tbx1 genetically interacts with Fgf8: Fgf8 expression is abolished in the pharyngeal endoderm of Tbx1-null mutants, and double heterozygous Tbx1+/-;Fgf8+/- mice show significantly higher penetrance of aortic arch artery defects than either single heterozygote, establishing a genetic link between Tbx1 and FGF signaling. In situ hybridization, genetic intercross of Tbx1 and Fgf8 mutant mice Development (Cambridge, England) High 12223416
2003 TBX1 is regulated by tissue-specific forkhead (Fox) transcription factors (Foxa2, Foxc1, Foxc2) through a single cis-element upstream of Tbx1 that is essential for its transcription in pharyngeal endoderm and head mesenchyme; this regulatory region is also responsive to Shh signaling in vivo. Enhancer reporter assays, transgenic mice, Shh loss-of-function, ChIP/binding assays for Fox proteins Genes & development High 12533514
2000 TBX1 protein binds a palindromic T-box oligonucleotide as a dimer in vitro but has no effect on transcription of a chimeric reporter plasmid in the assay used, in contrast to TBX2 (repressor) and Xbra/T (activator), demonstrating that TBX1 DNA binding does not inherently drive strong transcriptional activation or repression through T-box elements. In vitro DNA binding assays, transcriptional reporter assays Gene Medium 11111039
2004 Tbx1 has a dual role in cardiac outflow tract morphogenesis: (1) it supports cell proliferation in the secondary heart field, and (2) it is required in Nkx2.5-expressing cells for formation of the aorto-pulmonary septum. Fgf10 is identified as a direct transcriptional target of Tbx1 in vitro. Tissue-specific deletion using Cre/loxP, cell proliferation assays, in vitro transcription activation assay for Fgf10 Development (Cambridge, England) High 15175244
2004 Tbx1 is required in pharyngeal mesoderm for branchiomeric myogenesis: in its absence, myogenic determination genes Myf5 and MyoD fail to be normally activated in pharyngeal mesoderm, while Capsulin/MyoR-expressing unspecified precursor cells persist. Tbx1 null mouse analysis, in situ hybridization for myogenic markers Human molecular genetics High 15385444
2004 Tbx1 regulates FGF signaling in an autoregulatory loop in the anterior heart field: a Fox-binding site upstream of Tbx1 interacts with Foxa2 in pharyngeal mesoderm, and Tbx1 itself regulates an Fgf8 enhancer in the cardiac outflow tract; Tbx1 gain-of-function expands Fgf10-marked outflow tract myocardium. Tbx1 allelic series (hypomorphic mice), enhancer reporter assays, in vivo gain-of-function transgenic mice Development (Cambridge, England) High 15469978
2005 Tbx1 function in fourth pharyngeal arch artery development is cell non-autonomous and requires expression specifically in pharyngeal epithelia; Tbx1 is also expressed in endothelial cell precursors of pharyngeal arch arteries. Cell fate mapping, tissue-specific Cre-mediated deletion using six Cre lines Development (Cambridge, England) High 16284121
2005 Retinoic acid (RA) down-regulates Tbx1 expression in vivo and in vitro in a dose-dependent manner, independently of the Shh/Foxa2 regulatory pathway, placing RA as an upstream repressor of Tbx1. Vitamin A-deficient quail model, RA bead grafts in chick, real-time PCR of RA-treated P19 cells, protein synthesis inhibitor experiments Developmental dynamics High 15736167
2005 Tbx1 is required throughout pharyngeal segmentation for regulation of endoderm expansion, as defined by timed Cre-mediated deletion revealing distinct time windows for each pharyngeal derivative. Timed Cre-mediated deletion, cell fate mapping in mouse Development (Cambridge, England) High 16141220
2006 Mesodermal expression of Tbx1 is both necessary and sufficient for pharyngeal arch and cardiac outflow tract development; Tbx1 in mesoderm is required to sustain cell proliferation; restoration of mesodermal Tbx1 in null background rescues most pharyngeal and cardiovascular defects. Mesoderm-specific Cre deletion and transgenic rescue in mouse Development (Cambridge, England) High 16914493
2006 Tbx1 expression in pharyngeal endoderm is required for patterning and development of the pharyngeal apparatus and its derivatives; loss of Tbx1 in pharyngeal endoderm blocks pharyngeal pouch outgrowth. Cre/loxP conditional knockout using Foxg1-Cre for pharyngeal endoderm-specific ablation in mouse Development (Cambridge, England) High 16452092
2006 Tbx1 haploinsufficiency causes prepulse inhibition (PPI) deficits, a schizophrenia endophenotype; single-gene Tbx1+/- mice are sufficient to produce this behavioral phenotype, linking Tbx1 to psychiatric features of 22q11DS. Mouse behavioral assays (PPI), defined mouse mutant panel with overlapping deletions, human family mutation analysis Proceedings of the National Academy of Sciences of the United States of America High 16684884
2006 Tbx1 and Crkl (22q11 genes) interact in a dose-dependent manner to control pharyngeal segmentation and patterning along the anteroposterior axis; compound heterozygosity causes increased penetrance of DiGeorge-like phenotype; local regulation of retinoic acid metabolism is disrupted; partial rescue achieved by genetically reducing RA production. Genetic intercross of Tbx1 and Crkl mutant mice, genetic reduction of RA (Raldh2 heterozygosity), phenotypic analysis Developmental cell High 16399080
2006 Tbx1 is regulated in the secondary heart field by forkhead (Fox) proteins through two evolutionarily conserved Fox-binding sites; SHF-derived Tbx1-expressing cells (fate-mapped by the Tbx1 enhancer) contribute to right ventricular infundibulum, pulmonary trunk, and pulmonary valves. Enhancer reporter assays with conserved Fox binding site mutations, cell fate analysis using Tbx1 enhancer-driven Cre in mouse Developmental dynamics High 16444712
2006 Cyp26a1, Cyp26b1, and Cyp26c1 (retinoic acid-degrading enzymes) are down-regulated in Tbx1 null pharyngeal tissues, placing Cyp26 genes downstream of Tbx1; inhibition of Cyp26 enzyme function in chick phenocopies DiGeorge syndrome, linking Tbx1-dependent RA catabolism to pharyngeal development. Real-time PCR and in situ hybridization in Tbx1 null mice, pharmacological Cyp26 inhibition (R115866) in chick embryos Human molecular genetics High 17047027
2006 Tbx1 binds to a Pitx2 cardiac enhancer (containing a T-half site near an Nkx2.5-binding site) in vitro and activates it synergistically with Nkx2.5; Tbx1 co-expressed with Pitx2 in secondary heart field; Tbx1+/-;Pitx2+/- double heterozygotes die perinatally with cardiac defects. In vitro binding and transcriptional assays, genetic intercross, in situ hybridization Development (Cambridge, England) High 16556915
2007 Fate mapping using Tbx1Cre knock-in reveals that Tbx1-expressing cell descendants constitute a mesodermal population surrounding the primitive pharynx that populates most of the outflow tract (excluding the anterior portion) including both myocardial and endocardial layers, suggesting a common origin. Tbx1Cre knock-in allele, reporter-based fate mapping, 3D image reconstruction in mouse Genesis High 17610275
2008 Tbx1 controls cardiac neural crest cell migration to caudal pharyngeal arch arteries non-autonomously by regulating Gbx2 expression in the pharyngeal surface ectoderm; Gbx2 downstream of Tbx1 triggers directional cues to cardiac NCCs; Slit/Robo signaling components are affected in Gbx2 and Tbx1 mutants. Genetic approaches (conditional deletion, ectodermal Cre), NCC migration analysis, molecular marker analysis in mouse Development (Cambridge, England) High 19700621
2008 Tbx1 is required for the development of subpulmonary myocardium at the base of the pulmonary trunk; Semaphorin3c is identified as a Tbx1-dependent gene expressed in subpulmonary myocardium; loss of Tbx1 causes anomalous coronary artery patterning. Genetic crosses using transgene markers of second heart field myocardium and coronary endothelial cells, gene expression analysis in Tbx1 mutant mice Circulation research High 18583714
2008 Tbx1 and Brn4 cooperate in the periotic mesenchyme for cochlear formation; Brn4 expression is reduced in Tbx1 null mutants; Brn4-;Tbx1+/- double mutants show more severe cochlear defects (Mondini dysplasia) than either single mutant. Generation and analysis of double-mutant mice (Brn4-;Tbx1+/-), inner ear phenotyping Journal of the Association for Research in Otolaryngology Medium 18231833
2009 Tbx1 is expressed in multipotent cardiac progenitor cells (CPCs) of the second heart field; it stimulates CPC proliferation and inhibits differentiation; Tbx1 binds serum response factor (SRF) and negatively regulates its levels; loss of Tbx1 causes premature differentiation while gain prevents differentiation in vivo. Clonal analysis, loss- and gain-of-function models in vivo and in vitro, Co-immunoprecipitation (Tbx1-SRF binding) Circulation research High 19745164
2009 Tbx1 regulates the BMP-Smad1 signaling pathway in a transcription-independent manner: Tbx1 physically binds Smad1 (Co-IP), suppresses Bmp4/Smad1 signaling, and interferes with Smad1-Smad4 binding. A TBX1 mutation that abolishes transactivation does not affect Smad1 binding; a disease-associated TBX1 mutation that does not prevent transactivation blocks TBX1-SMAD1 interaction. Tbx1 gain-of-function in transgenic mice generates phenotypes similar to loss of a Bmp receptor. Co-immunoprecipitation, transactivation assays with separation-of-function mutants, transgenic mice with Tbx1 gain-of-function and Smad1 transgenic rescue PloS one High 19557177
2009 Tbx1 requires biallelic expression in pharyngeal ectoderm together with Chd7 for normal fourth pharyngeal arch artery development; Tbx1+/-;Chd7+/- double heterozygotes show synergistic interaction affecting fourth PAA, thymus, and ear morphogenesis; neural crest-specific Chd7 rescue did not restore PAA morphogenesis. Double heterozygous mouse crosses, tissue-specific neural crest Chd7 rescue experiments, arch artery phenotyping The Journal of clinical investigation High 19855134
2009 Tbx1 controls pharyngeal pouch morphogenesis in zebrafish through mesodermal wnt11r and fgf8a: Tbx1 promotes pouch-forming endoderm morphogenesis through these mesodermal signals; compound loss of wnt11r and fgf8a phenocopies tbx1 mutant pouch defects; 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 (Cambridge, England) High 25142463
2010 Tbx1 activates Vegfr3 transcription in endothelial cells by binding to an enhancer element in the Vegfr3 gene; conditional deletion of Tbx1 in endothelial cells causes widespread lymphangiogenesis defects in mice; Tbx1 is required for growth and maintenance, but not differentiation, of lymphatic endothelial cells. Molecular (enhancer binding assays), conditional endothelial-specific Tbx1 knockout, lymphatic vessel phenotyping The Journal of cell biology High 20439995
2010 Ash2l (component of a histone methyltransferase complex) physically interacts with Tbx1 in both yeast and mammalian cells and acts as a transcriptional co-activator in luciferase reporter assays; Tbx1 and Ash2l have overlapping expression during development. Yeast two-hybrid screen, Co-immunoprecipitation in mammalian cells, luciferase reporter assays, Ash2l knockout mouse Experimental biology and medicine Medium 20463296
2010 Tbx1 negatively regulates Pitx2 transcriptional activity; Tbx1 physically interacts with the PITX2 C-terminus and represses PITX2 activation of p21, LEF-1, and Pitx2c promoters; this mechanism controls cell proliferation in dental epithelium. Tbx1(-/+)/Pitx2(-/+) double heterozygous mice show extra premolar-like teeth, confirming genetic interaction. Co-immunoprecipitation, luciferase reporter assays, chromatin immunoprecipitation, conditional knockout mice, double heterozygous mouse analysis Developmental biology High 20816801
2011 Six1 and Eya1 genetically interact with Tbx1 in a Tbx1-Six1/Eya1-Fgf8 pathway controlling cardiovascular and craniofacial morphogenesis; Fgf8 is a direct downstream effector of Six1 and Eya1; Six1/Eya1 double mutants recapitulate del22q11 features. Mouse genetic intercrosses, gene expression analysis, direct target identification The Journal of clinical investigation High 21364285
2011 Tbx1 downstream pathway in the second heart field includes Isl1 (downregulated in Tbx1 null); Tbx1 positively regulates SHF cell proliferation and negatively regulates differentiation; pan-mesodermal ablation of Tbx1 causes cell-autonomous gene expression changes; opposite changes occur in TBX1 gain-of-function mutants. Gene expression profiling, pan-mesodermal Tbx1 ablation (T-Cre), TBX1 gain-of-function transgenic mice Developmental biology High 18328475
2011 Ripply3 suppresses Tbx1 transcriptional activation activity in luciferase assays; Ripply3 represses Tbx1-induced Pax9 expression; Ripply3-deficient mice have pharyngeal defects and upregulated Pax9, consistent with relief of Tbx1 repression. Luciferase reporter assays, Ripply3 knockout mouse, in situ hybridization for Pax9 Development (Cambridge, England) High 21177346
2011 Tbx1 loss reduces Hes1 expression in Tbx1-expressing lineages; Hes1 (Notch signaling effector) mutant mice have 22q11DS-like defects; conditional Hes1 inactivation in pharyngeal ectoderm (like Tbx1) causes thymus and PAA defects, placing Hes1 downstream of Tbx1. FACS-Gal sorting of Tbx1-expressing cells, expression profiling, Hes1 conditional knockout in pharyngeal ectoderm Developmental biology High 20122914
2012 The histone acetyltransferase MOZ complex occupies the Tbx1 locus, promotes Tbx1 expression and histone 3 lysine 9 acetylation; Moz null mice phenocopy DiGeorge syndrome; Moz and Tbx1 genetically interact (Moz+/-;Tbx1+/- mice show enhanced phenotype); a Tbx1 transgene rescues heart phenotype in Moz mutants. ChIP for MOZ at the Tbx1 locus, MOZ knockout and heterozygous mouse analysis, Tbx1 transgenic rescue Developmental cell High 22921202
2012 Tbx1 directly regulates Fgf10 expression in anterior second heart field cells through a 1.7-kb intronic region; Tbx1 ChIP binding at this region is demonstrated in vivo. Transgenic reporter assay of Fgf10 1.7-kb intronic element, ChIP for Tbx1 at Fgf10 locus Proceedings of the National Academy of Sciences of the United States of America High 23093675
2012 Tbx1 is a negative modulator of Mef2c: Mef2c expression is negatively correlated with Tbx1 dosage in the second heart field; Tbx1 occupies conserved regulatory regions of the Mef2c locus (ChIP); Tbx1 also interferes with the Gata4→Mef2c regulatory pathway. Microarray transcriptome analysis across Tbx1 allelic series, in situ hybridization, Tbx1 gain-of-function analysis, ChIP Human molecular genetics High 22367967
2012 Tbx1 acts upstream of Smad7 in pharyngeal arch artery remodeling: Smad7 expression is regulated by Tbx1, and Tbx1;Smad7 compound haploinsufficiency impairs vascular smooth muscle cell coverage and fibronectin deposition in the fourth arch artery; Tbx1Cre-driven conditional Smad7 reconstitution shows the interaction is cell autonomous. Tbx1/Smad7 double heterozygous mouse crosses, conditional Smad7 reconstitution with Tbx1Cre, vascular phenotyping Circulation research High 23011393
2013 Tbx1 regulates brain angiogenesis in a cell-autonomous manner in endothelial cells; TBX1 regulates DLL4 and VEGFR3 genes in brain endothelial cells; EC-specific Tbx1 conditional mutants have brain vessel hyperplasia, enhanced sprouting, and network disorganization; a Notch1 agonist partially rescues microtubule hyperbranching caused by TBX1 knockdown, placing TBX1 upstream of DLL4/Notch1-VEGFR3 axis. EC-specific conditional Tbx1 knockout, 3D EC-matrigel culture system, Notch1 agonist rescue experiment Human molecular genetics High 23945394
2013 In zebrafish, tbx1 regulates heart looping and cardiomyocyte differentiation through wnt11r (non-canonical Wnt) and alcama (activated leukocyte cell adhesion molecule a); wnt11r and alcama are downregulated in tbx1 null; ectopic expression of wnt11r or alcama partially rescues tbx1 mutant heart looping defects. Zebrafish tbx1 null analysis, gene expression studies, morpholino knockdown, mRNA rescue injection PloS one High 23533583
2014 Tbx1 is required for inflow as well as outflow tract morphogenesis by regulating segregation and deployment of posterior second heart field progenitor cells; in Tbx1 null embryos, OFT progenitor cells fail to segregate from the posterior SHF progenitor pool; addition of SHF cells to the venous pole is also impaired, causing atrioventricular septal defects. Transcriptome analysis, genetic tracing with Tbx1Cre and SHF markers, fluorescent dye labeling in mouse embryos Circulation research High 25190705
2014 TBX1 regulates epithelial polarity and dynamic basal filopodia in second heart field cells; Tbx1 null SHF cells show increased circularity, reduced basolateral membrane domain, impaired filopodial activity, and elevated aPKCζ levels; aPKCζ activation phenocopies Tbx1 null proliferative and differentiation defects. Immunofluorescence, live imaging, embryo culture, aPKCζ activation in embryo culture Development (Cambridge, England) High 25371366
2014 Pax9 is downstream of Tbx1 in pharyngeal endoderm; Tbx1/Pax9 double heterozygous mice have significantly increased incidence of interrupted aortic arch; using Pax9Cre, the site of interaction is defined as the pharyngeal endoderm. Tbx1/Pax9 double heterozygous mouse crosses, Pax9Cre conditional allele, transcriptome analysis Development (Cambridge, England) High 31444215
2015 TBX1 interacts with PITX2 to negatively regulate PITX2 transcriptional activity; miR-96-5p represses TBX1 expression and TBX1 represses miR-96, forming a regulatory loop; TBX1 regulates dental progenitor cell proliferation through miR-96-5p and PITX2; human TBX1 disease mutations show functional differences in transcriptional regulation of miR-96 and co-regulation of PITX2. Conditional Tbx1 knockout/overexpression in dental epithelium, lineage tracing, luciferase assays, miR-96 manipulation, Co-IP of TBX1 and PITX2 Human molecular genetics High 25556186
2019 Tbx1 is required to maintain integrity of extracellular matrix (ECM)-integrin-focal adhesion (FA) signaling in the second heart field; loss of TBX1 impairs ECM-integrin-FA signaling, cell migration, and focal adhesions in vivo and in cultured cells; this function is non-cell autonomous in embryos; interfering with the ECM-integrin-FA axis during the Tbx1-required time window (E8.5-E9.5) causes outflow tract dysmorphogenesis. Mouse embryo analysis, cultured cell loss-of-function, mosaic analysis, integrin/FA signaling assays Human molecular genetics High 31180501
2019 TBX1 functions as a tumor suppressor in thyroid cancer cells by inhibiting PI3K/AKT and MAPK/ERK pathways; ectopic TBX1 expression inhibits AKT phosphorylation at Ser473 and ERK phosphorylation via downstream targets RNF41, PARK2, and PHLPP2; TBX1 promoter is frequently methylated in thyroid cancer. ChIP-sequencing, dual-luciferase reporter assays, ectopic expression and knockdown in thyroid cancer cells, in vitro and in vivo (nude mouse) functional assays Thyroid Medium 30543152
2021 Single-cell RNA-sequencing identifies a Tbx1-marked multilineage primed (MLP) progenitor population within cardiopharyngeal mesoderm with bipotent cardiac and branchiomeric muscle properties; Tbx1 regulates maturation of MLP cells while restricting ectopic non-mesodermal gene expression; TBX1 acts partly through altering chromatin accessibility of enriched genes in MLP cells. Single-cell RNA-sequencing, ATAC-seq (chromatin accessibility), genetic tracing in mouse Nature communications High 34789765
2023 Single-cell RNA-sequencing of Tbx1 null and control mouse embryos reveals three dynamic transitions of pharyngeal NCCs through differentiated CNCCs; loss of Tbx1 non-autonomously disrupts these transitions by altering mesoderm-to-CNCC cell-cell communication, upregulating/prematurely activating BMP signaling, reducing MAPK signaling, and disrupting aortic arch artery formation and cardiac outflow tract septation. Single-cell RNA-sequencing of Tbx1 null and control pharyngeal apparatus + heart tissues, cell-cell communication analysis Nature communications High 36941249
2023 TBX1 in lymphatic endothelial cells drives an immunosuppressive program post-myocardial infarction; Tbx1-activated LECs penetrate the infarcted area and promote tolerogenic dendritic cells and regulatory T cells through Ccl21 and Icam1, thereby suppressing autoreactive CD8+ T cells and facilitating post-MI repair. Conditional Tbx1 knockout in LECs, scRNA-seq, immunofluorescence, cell transfer experiments, post-MI mouse models Immunity High 37625409

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 770 11242049
2020 Dsuite - Fast D-statistics and related admixture evidence from VCF files. Molecular ecology resources 652 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
2004 Tbx1 has a dual role in the morphogenesis of the cardiac outflow tract. Development (Cambridge, England) 298 15175244
2002 Tbx1 mutation causes multiple cardiovascular defects and disrupts neural crest and cranial nerve migratory pathways. Human molecular genetics 267 11971873
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 238 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
2003 Tbx1 is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancer. Genes & development 206 12533514
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 196 35639788
2004 Tbx1 regulates fibroblast growth factors in the anterior heart field through a reinforcing autoregulatory loop involving forkhead transcription factors. Development (Cambridge, England) 181 15469978
2006 Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Developmental cell 162 16399080
2006 Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development (Cambridge, England) 151 16914493
1997 Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene. Genomics 126 9268629
2006 Inactivation of Tbx1 in the pharyngeal endoderm results in 22q11DS malformations. Development (Cambridge, England) 123 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 119 19745164
2009 Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. The Journal of clinical investigation 118 19855134
2006 Tbx1 affects asymmetric cardiac morphogenesis by regulating Pitx2 in the secondary heart field. Development (Cambridge, England) 117 16556915
2011 A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. The Journal of clinical investigation 113 21364285
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
2005 Tbx1 expression in pharyngeal epithelia is necessary for pharyngeal arch artery development. Development (Cambridge, England) 110 16284121
2008 Identification of downstream genetic pathways of Tbx1 in the second heart field. Developmental biology 109 18328475
2003 TBX1 is required for inner ear morphogenesis. Human molecular genetics 106 12913075
2005 Timed mutation and cell-fate mapping reveal reiterated roles of Tbx1 during embryogenesis, and a crucial function during segmentation of the pharyngeal system via regulation of endoderm expansion. Development (Cambridge, England) 102 16141220
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 92 25190705
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
2006 Cyp26 genes a1, b1 and c1 are down-regulated in Tbx1 null mice and inhibition of Cyp26 enzyme function produces a phenocopy of DiGeorge Syndrome in the chick. Human molecular genetics 86 17047027
2012 MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Developmental cell 84 22921202
2007 A fate map of Tbx1 expressing cells reveals heterogeneity in the second cardiac field. Genesis (New York, N.Y. : 2000) 84 17610275
2000 Differential DNA binding and transcription modulation by three T-box proteins, T, TBX1 and TBX2. Gene 75 11111039
2011 Tbx1: identification of a 22q11.2 gene as a risk factor for autism spectrum disorder in a mouse model. Human molecular genetics 73 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 67 17117436
2010 Tbx1 regulates Vegfr3 and is required for lymphatic vessel development. The Journal of cell biology 65 20439995
2013 NK4 antagonizes Tbx1/10 to promote cardiac versus pharyngeal muscle fate in the ascidian second heart field. PLoS biology 62 24311985
2011 Identification of a Tbx1/Tbx2/Tbx3 genetic pathway governing pharyngeal and arterial pole morphogenesis. Human molecular genetics 62 22116936
2006 Tbx1 is regulated by forkhead proteins in the secondary heart field. Developmental dynamics : an official publication of the American Association of Anatomists 61 16444712
2005 Tbx1 is required for proper neural crest migration and to stabilize spatial patterns during middle and inner ear development. Mechanisms of development 59 15652707
2014 TBX1 regulates epithelial polarity and dynamic basal filopodia in the second heart field. Development (Cambridge, England) 58 25371366
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 54 17377518
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
2012 Tbx1 regulates oral epithelial adhesion and palatal development. Human molecular genetics 50 22371266
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
2007 Deletion of the Pitx1 genomic locus affects mandibular tooth morphogenesis and expression of the Barx1 and Tbx1 genes. Developmental biology 50 18082678
2023 Lymphatic endothelial transcription factor Tbx1 promotes an immunosuppressive microenvironment to facilitate post-myocardial infarction repair. Immunity 49 37625409
2014 TBX1 mutation identified by exome sequencing in a Japanese family with 22q11.2 deletion syndrome-like craniofacial features and hypocalcemia. PloS one 49 24637876
2006 Tbx1 regulates population, proliferation and cell fate determination of otic epithelial cells. Developmental biology 49 17074316
2011 Her9 represses neurogenic fate downstream of Tbx1 and retinoic acid signaling in the inner ear. Development (Cambridge, England) 48 21205785
2006 The 22q11 deletion syndrome candidate gene Tbx1 determines thyroid size and positioning. Human molecular genetics 48 17164259
2004 Developmental expression of the amphioxus Tbx1/ 10 gene illuminates the evolution of vertebrate branchial arches and sclerotome. Development genes and evolution 48 15372236
2011 Ripply3, a Tbx1 repressor, is required for development of the pharyngeal apparatus and its derivatives in mice. Development (Cambridge, England) 47 21177346
2015 TBX1 protein interactions and microRNA-96-5p regulation controls cell proliferation during craniofacial and dental development: implications for 22q11.2 deletion syndrome. Human molecular genetics 44 25556186
2021 Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm. Nature communications 43 34789765
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
2013 Understanding the role of Tbx1 as a candidate gene for 22q11.2 deletion syndrome. Current allergy and asthma reports 42 23996541
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
2006 Fgf8 expression in the Tbx1 domain causes skeletal abnormalities and modifies the aortic arch but not the outflow tract phenotype of Tbx1 mutants. Developmental biology 41 16696966
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 40 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 Mesodermal Tbx1 is required for patterning the proximal mandible in mice. Developmental biology 36 20501333
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
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 32 25860641
2009 Tbx1 and Brn4 regulate retinoic acid metabolic genes during cochlear morphogenesis. BMC developmental biology 31 19476657
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
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 29 34737458
2019 Tbx1 and Foxi3 genetically interact in the pharyngeal pouch endoderm in a mouse model for 22q11.2 deletion syndrome. PLoS genetics 29 31412026
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
2012 Tbx1 is a negative modulator of Mef2c. Human molecular genetics 29 22367967
2023 Single-cell transcriptomics uncovers a non-autonomous Tbx1-dependent genetic program controlling cardiac neural crest cell development. Nature communications 28 36941249
2016 Rewiring of an ancestral Tbx1/10-Ebf-Mrf network for pharyngeal muscle specification in distinct embryonic lineages. Development (Cambridge, England) 28 27802138
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
2020 Relationship Between Severity of T Cell Lymphopenia and Immune Dysregulation in Patients with DiGeorge Syndrome (22q11.2 Deletions and/or Related TBX1 Mutations): a USIDNET Study. Journal of clinical immunology 27 32949294
2019 Tbx1 regulates extracellular matrix-cell interactions in the second heart field. Human molecular genetics 27 31180501
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

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