t box domain proteins


Summary: Proteins containing a region of conserved sequence, about 200 amino acids long, which encodes a particular sequence specific DNA binding domain (the T-box domain). These proteins are transcription factors that control developmental pathways. The prototype of this family is the mouse Brachyury (or T) gene product.

Top Publications

  1. Calmont A, Ivins S, van Bueren K, Papangeli I, Kyriakopoulou V, Andrews W, et al. Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm. Development. 2009;136:3173-83 pubmed publisher
    ..We propose that the spatiotemporal control of this tightly orchestrated network of genes participates in crucial aspects of PAA development...
  2. Brill M, Ninkovic J, Winpenny E, Hodge R, Ozen I, Yang R, et al. Adult generation of glutamatergic olfactory bulb interneurons. Nat Neurosci. 2009;12:1524-33 pubmed publisher
    ..Taken together, our data indicate that SEZ progenitors not only produce a population of adult-born glutamatergic juxtaglomerular neurons, but may also provide a previously unknown source of progenitors for endogenous repair. ..
  3. Choi M, Klingensmith J. Chordin is a modifier of tbx1 for the craniofacial malformations of 22q11 deletion syndrome phenotypes in mouse. PLoS Genet. 2009;5:e1000395 pubmed publisher
    ..Thus, chordin is a modifier for the craniofacial anomalies of Tbx1 mutations, demonstrating the existence of a second-site modifier for a specific subset of the phenotypes associated with 22q11DS. ..
  4. Kowalczyk T, Pontious A, Englund C, Daza R, Bedogni F, Hodge R, et al. Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex. Cereb Cortex. 2009;19:2439-50 pubmed publisher
    ..Our findings support the hypothesis that regulated amplification of INPs may be an important factor controlling the balance of neurogenesis among different cortical layers. ..
  5. Garnett A, Han T, Gilchrist M, Smith J, Eisen M, Wardle F, et al. Identification of direct T-box target genes in the developing zebrafish mesoderm. Development. 2009;136:749-60 pubmed publisher
    ..We also find that deltaD is directly activated by T-box factors in the tail bud, where it has been implicated in starting the segmentation clock, suggesting that spt and ntl act upstream of this process. ..
  6. Cruz Guilloty F, Pipkin M, Djuretic I, Levanon D, Lotem J, Lichtenheld M, et al. Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. J Exp Med. 2009;206:51-9 pubmed publisher
    ..Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs. ..
  7. Intlekofer A, Banerjee A, Takemoto N, Gordon S, Dejong C, Shin H, et al. Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science. 2008;321:408-11 pubmed publisher
    ..T-bet and Eomes, thus, ensure that CD8+ T cells adopt an appropriate course of intracellular rather than extracellular destruction. ..
  8. Postma A, van de Meerakker J, Mathijssen I, Barnett P, Christoffels V, Ilgun A, et al. A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation. Circ Res. 2008;102:1433-42 pubmed publisher
  9. Wardle F, Papaioannou V. Teasing out T-box targets in early mesoderm. Curr Opin Genet Dev. 2008;18:418-25 pubmed publisher

More Information


  1. Schulz E, Mariani L, Radbruch A, Hofer T. Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Immunity. 2009;30:673-83 pubmed publisher
    ..Thus initial polarization and subsequent imprinting of Th1 cells are mediated by interlinked, sequentially acting positive feedback loops of TCR-interferon-gamma-Stat1-T-bet and interleukin-12-Stat4-T-bet signaling. ..
  2. Gocke A, Hussain R, Yang Y, Peng H, Weiner J, Ben L, et al. Transcriptional modulation of the immune response by peroxisome proliferator-activated receptor-{alpha} agonists in autoimmune disease. J Immunol. 2009;182:4479-87 pubmed publisher
    ..Finally, therapeutic administration of PPARalpha agonists ameliorated clinically established EAE, suggesting that PPARalpha agonists may provide a treatment option for immune-mediated inflammatory diseases. ..
  3. Roybon L, Deierborg T, Brundin P, Li J. Involvement of Ngn2, Tbr and NeuroD proteins during postnatal olfactory bulb neurogenesis. Eur J Neurosci. 2009;29:232-43 pubmed publisher
    ..Taken together, our data illustrate that Ngn2, neuroD and Tbr transcription factors are involved in postnatal neurogenesis in the olfactory bulb. ..
  4. Miller S, Huang A, Miazgowicz M, Brassil M, Weinmann A. Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expression. Genes Dev. 2008;22:2980-93 pubmed publisher
    ..These novel mechanisms for T-box-mediated epigenetic regulation are essential, because point mutations that disrupt these interactions are found in a diverse array of human developmental genetic diseases. ..
  5. Furuta S, Kagami S, Tamachi T, Ikeda K, Fujiwara M, Suto A, et al. Overlapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic airway inflammation. J Immunol. 2008;180:6656-62 pubmed
    ..These results indicate that STAT4 not only plays an indispensable role in T-bet-independent Th1 differentiation but also is involved in the maintenance of Th17 cells and the enhancement of allergic airway inflammation. ..
  6. Boogerd K, Wong L, Christoffels V, Klarenbeek M, Ruijter J, Moorman A, et al. Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43. Cardiovasc Res. 2008;78:485-93 pubmed publisher
    ..Msx1 and Msx2 can function in concert with the T-box proteins to suppress Cx43 and other working myocardial genes. ..
  7. Ochiai W, Nakatani S, Takahara T, Kainuma M, Masaoka M, Minobe S, et al. Periventricular notch activation and asymmetric Ngn2 and Tbr2 expression in pair-generated neocortical daughter cells. Mol Cell Neurosci. 2009;40:225-33 pubmed publisher
    ..Many of the nascent cells exhibited pin-like morphology with a short ventricular process, suggesting periventricular presentation of Notch ligands to these cells. ..
  8. Randall V, McCue K, Roberts C, Kyriakopoulou V, Beddow S, Barrett A, et al. Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. J Clin Invest. 2009;119:3301-10 pubmed publisher
    ..We could not rescue PAA morphogenesis by restoring neural crest Chd7 expression. Rather, biallelic expression of Chd7 and Tbx1 in the pharyngeal ectoderm was required for normal PAA development...
  9. Macindoe I, Glockner L, Vukasin P, Stennard F, Costa M, Harvey R, et al. Conformational stability and DNA binding specificity of the cardiac T-box transcription factor Tbx20. J Mol Biol. 2009;389:606-18 pubmed publisher
    ..Our data highlight unique features of Tbx20 and suggest mechanistic ways in which cardiac T-box factors might interact synergistically and/or competitively within the cardiac regulatory network. ..
  10. Hammer S, Toenjes M, Lange M, Fischer J, Dunkel I, Mebus S, et al. Characterization of TBX20 in human hearts and its regulation by TFAP2. J Cell Biochem. 2008;104:1022-33 pubmed publisher
    ..In summary, we provide first insights into the regulation of TBX20 and show its potential for human congenital heart diseases. ..
  11. BURNS C, Galloway J, Smith A, Keefe M, Cashman T, Paik E, et al. A genetic screen in zebrafish defines a hierarchical network of pathways required for hematopoietic stem cell emergence. Blood. 2009;113:5776-82 pubmed publisher
    ..Together, our results establish a hierarchy of signaling programs required and sufficient for HSC emergence in the AGM. ..
  12. Liao J, Aggarwal V, Nowotschin S, Bondarev A, Lipner S, Morrow B. Identification of downstream genetic pathways of Tbx1 in the second heart field. Dev Biol. 2008;316:524-37 pubmed publisher
    ..When taken together, our studies show that Tbx1 acts upstream in a genetic network that positively regulates SHF cell proliferation and negatively regulates differentiation, cell-autonomously in the caudal pharyngeal region. ..
  13. Vormer T, Foijer F, Wielders C, te Riele H. Anchorage-independent growth of pocket protein-deficient murine fibroblasts requires bypass of G2 arrest and can be accomplished by expression of TBX2. Mol Cell Biol. 2008;28:7263-73 pubmed publisher
    ..Since transformation of human fibroblasts also requires ablation of both pathways, our results imply that the mechanisms underlying transformation of human and mouse cells are not as different as previously claimed. ..
  14. Liu C, Shen A, Li X, Jiao W, Zhang X, Li Z. T-box transcription factor TBX20 mutations in Chinese patients with congenital heart disease. Eur J Med Genet. 2008;51:580-7 pubmed publisher
    ..The findings provide the first insight into TBX20 mutations for TOF and TAPVC. Functional study involved in the new sequence variants should be subject of further investigation. ..
  15. Hitachi K, Danno H, Tazumi S, Aihara Y, Uchiyama H, Okabayashi K, et al. The Xenopus Bowline/Ripply family proteins negatively regulate the transcriptional activity of T-box transcription factors. Int J Dev Biol. 2009;53:631-9 pubmed publisher
    ..We conclude that although the Xenopus Bowline/Ripply family proteins Bowline, Ledgerline and xRipply3 are expressed differentially, they all act as negative regulators of T-box proteins. ..
  16. Martin B, Kimelman D. Regulation of canonical Wnt signaling by Brachyury is essential for posterior mesoderm formation. Dev Cell. 2008;15:121-33 pubmed publisher
    ..We propose that a positive autoregulatory loop between Ntl/Bra and canonical Wnt signaling maintains the mesodermal progenitors to facilitate posterior somite development in chordates...
  17. Tazumi S, Yabe S, Yokoyama J, Aihara Y, Uchiyama H. PMesogenin1 and 2 function directly downstream of Xtbx6 in Xenopus somitogenesis and myogenesis. Dev Dyn. 2008;237:3749-61 pubmed publisher
  18. Sessa A, Mao C, Hadjantonakis A, Klein W, Broccoli V. Tbr2 directs conversion of radial glia into basal precursors and guides neuronal amplification by indirect neurogenesis in the developing neocortex. Neuron. 2008;60:56-69 pubmed publisher
    ..Together, these findings identify Tbr2 as a critical factor for the specification of IPCs during corticogenesis. ..
  19. Rodriguez M, Aladowicz E, Lanfrancone L, Goding C. Tbx3 represses E-cadherin expression and enhances melanoma invasiveness. Cancer Res. 2008;68:7872-81 pubmed publisher
  20. Grifone R, Jarry T, Dandonneau M, Grenier J, Duprez D, Kelly R. Properties of branchiomeric and somite-derived muscle development in Tbx1 mutant embryos. Dev Dyn. 2008;237:3071-8 pubmed publisher
    ..The critical requirement for Tbx1 during muscle development is thus in the robust onset of myogenic specification in pharyngeal mesoderm. ..
  21. Arnold S, Huang G, Cheung A, Era T, Nishikawa S, Bikoff E, et al. The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone. Genes Dev. 2008;22:2479-84 pubmed publisher
    ..Neurogenesis in the adult dentate gyrus but not the subependymal zone is abolished. These studies establish Tbr2 as a key regulator of neurogenesis in the SVZ. ..
  22. Govoni K, Linares G, Chen S, Pourteymoor S, Mohan S. T-box 3 negatively regulates osteoblast differentiation by inhibiting expression of osterix and runx2. J Cell Biochem. 2009;106:482-90 pubmed publisher
  23. Morley R, Lachani K, Keefe D, Gilchrist M, Flicek P, Smith J, et al. A gene regulatory network directed by zebrafish No tail accounts for its roles in mesoderm formation. Proc Natl Acad Sci U S A. 2009;106:3829-34 pubmed publisher
    ..Using our genome-scale data we have assembled a preliminary gene regulatory network that begins to describe mesoderm formation and patterning in the early zebrafish embryo. ..
  24. Georges R, Nemer G, Morin M, Lefebvre C, Nemer M. Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation. Mol Cell Biol. 2008;28:4052-67 pubmed publisher
    ..The data may help analyze genotype-phenotype relations in patients with Holt-Oram syndrome. ..
  25. Qian L, Mohapatra B, Akasaka T, Liu J, Ocorr K, Towbin J, et al. Transcription factor neuromancer/TBX20 is required for cardiac function in Drosophila with implications for human heart disease. Proc Natl Acad Sci U S A. 2008;105:19833-8 pubmed publisher
    ..These findings suggest that the fly heart might serve as an identifier of candidate genes involved in human heart disease. ..
  26. Yang Y, Xu J, Niu Y, Bromberg J, Ding Y. T-bet and eomesodermin play critical roles in directing T cell differentiation to Th1 versus Th17. J Immunol. 2008;181:8700-10 pubmed
    ..Naive CD4 T cells deficient in Stat6 and T-bet also induce a Th17-dominant colitis development in vivo. Our data provide new insights into the choice between Th1 and Th17 development and their roles in autoimmunity. ..
  27. Kawamura A, Koshida S, Takada S. Activator-to-repressor conversion of T-box transcription factors by the Ripply family of Groucho/TLE-associated mediators. Mol Cell Biol. 2008;28:3236-44 pubmed publisher
    ..These results indicate that the intrinsic transcriptional property of T-box proteins is controlled by Ripply family proteins, which act as specific adaptors that recruit the global corepressor Groucho/TLE to T-box proteins. ..
  28. Yang Y, Weiner J, Liu Y, Smith A, Huss D, Winger R, et al. T-bet is essential for encephalitogenicity of both Th1 and Th17 cells. J Exp Med. 2009;206:1549-64 pubmed publisher
    ..These data suggest that encephalitogenicity of myelin-specific T cells appears to be mediated by a pathway dependent on T-bet and not necessarily pathway-specific end products, such as interferon gamma and IL-17. ..
  29. Pflugfelder G. omb and circumstance. J Neurogenet. 2009;23:15-33 pubmed publisher
    ..This review summarizes recent findings pertaining to omb and orthologous genes. ..
  30. Joshi N, Cui W, Chandele A, Lee H, Urso D, Hagman J, et al. Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity. 2007;27:281-95 pubmed
    ..These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential. ..
  31. Shen J, Dorner C, Bahlo A, Pflugfelder G. optomotor-blind suppresses instability at the A/P compartment boundary of the Drosophila wing. Mech Dev. 2008;125:233-46 pubmed publisher
    ..In the larval A/P fold, DE-cadherin-based adherens junctions appeared intact but the apical microtubule web was strongly reduced. ..
  32. Umemori M, Takemura M, Maeda K, Ohba K, Adachi Yamada T. Drosophila T-box transcription factor Optomotor-blind prevents pathological folding and local overgrowth in wing epithelium through confining Hh signal. Dev Biol. 2007;308:68-81 pubmed
    ..These are the mechanisms for generating secondary phenotypes when a single signaling factor Omb fails to function. ..
  33. Saka Y, Smith J. A mechanism for the sharp transition of morphogen gradient interpretation in Xenopus. BMC Dev Biol. 2007;7:47 pubmed
    ..It provides a mechanism by which a sharp boundary might be created between domains of different cell types in response to a morphogen gradient. ..
  34. Abrahams A, Mowla S, Parker M, Goding C, Prince S. UV-mediated regulation of the anti-senescence factor Tbx2. J Biol Chem. 2008;283:2223-30 pubmed
  35. Bielen H, Oberleitner S, Marcellini S, Gee L, Lemaire P, Bode H, et al. Divergent functions of two ancient Hydra Brachyury paralogues suggest specific roles for their C-terminal domains in tissue fate induction. Development. 2007;134:4187-97 pubmed publisher
    ..Our data support the concept of sub- and neofunctionalisation upon gene duplication and show that divergence of cis-regulation and coding sequence in paralogues can lead to dramatic changes in structure and function...
  36. Garrett W, Lord G, Punit S, Lugo Villarino G, Mazmanian S, Ito S, et al. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. 2007;131:33-45 pubmed
    ..These findings reveal a novel function for T-bet as a peacekeeper of host-commensal relationships and provide new perspectives on the pathophysiology of IBD. ..
  37. Xu H, Chen L, Baldini A. In vivo genetic ablation of the periotic mesoderm affects cell proliferation survival and differentiation in the cochlea. Dev Biol. 2007;310:329-40 pubmed
    ..This model provides a striking demonstration of the essential role played by the periotic mesenchyme in the organogenesis of the cochlea. ..
  38. Lewis M, Miller S, Miazgowicz M, Beima K, Weinmann A. T-bet's ability to regulate individual target genes requires the conserved T-box domain to recruit histone methyltransferase activity and a separate family member-specific transactivation domain. Mol Cell Biol. 2007;27:8510-21 pubmed
    ..The requirement for two separable functional activities may ultimately contribute to the stringent role for T-box proteins in establishing specific developmental gene expression pathways. ..
  39. Kirk E, Sunde M, Costa M, Rankin S, Wolstein O, Castro M, et al. Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Am J Hum Genet. 2007;81:280-91 pubmed
    ..They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up. ..
  40. Phoon R, Kitching A, Odobasic D, Jones L, Semple T, Holdsworth S. T-bet deficiency attenuates renal injury in experimental crescentic glomerulonephritis. J Am Soc Nephrol. 2008;19:477-85 pubmed publisher
    ..We conclude that T-bet directs Th1 responses that induce renal injury in experimental crescentic glomerulonephritis...
  41. Huynh T, Chen L, Terrell P, Baldini A. A fate map of Tbx1 expressing cells reveals heterogeneity in the second cardiac field. Genesis. 2007;45:470-5 pubmed
    ..Finally, we show that Tbx1(Cre)-positive and Tbx1(Cre)-negative cell descendants occupy discrete domains in the outflow tract throughout development. ..
  42. Braunstein E, Crenshaw E, Morrow B, Adams J. Cooperative function of Tbx1 and Brn4 in the periotic mesenchyme is necessary for cochlea formation. J Assoc Res Otolaryngol. 2008;9:33-43 pubmed publisher
  43. Suphapeetiporn K, Tongkobpetch S, Siriwan P, Shotelersuk V. TBX22 mutations are a frequent cause of non-syndromic cleft palate in the Thai population. Clin Genet. 2007;72:478-83 pubmed
    ..Our study indicates that TBX22 mutations are responsible for a significant proportion of Thai non-syndromic CP cases confirming its importance as a frequent cause of non-syndromic CP across different populations. ..
  44. Zhang Z, Baldini A. In vivo response to high-resolution variation of Tbx1 mRNA dosage. Hum Mol Genet. 2008;17:150-7 pubmed
    ..Overall, our data suggest that there are developmental process-specific gene dosage thresholds beyond which the phenotype worsens very rapidly with very small mRNA level reductions. ..
  45. Davis E, Teng H, Bilican B, Parker M, Liu B, Carriera S, et al. Ectopic Tbx2 expression results in polyploidy and cisplatin resistance. Oncogene. 2008;27:976-84 pubmed
    ..These results have important implications for our understanding of the role of Tbx2 in tumorigenesis because polyploidy frequently precedes aneuploidy, which is associated with high malignancy and poor prognosis. ..
  46. Andreou A, Pauws E, Jones M, Singh M, Bussen M, Doudney K, et al. TBX22 missense mutations found in patients with X-linked cleft palate affect DNA binding, sumoylation, and transcriptional repression. Am J Hum Genet. 2007;81:700-12 pubmed
    ..Thus, we suggest that SUMO modification may represent a common pathway that regulates normal craniofacial development and is involved in the pathogenesis of both Mendelian and idiopathic forms of orofacial clefting. ..
  47. Intlekofer A, Takemoto N, Kao C, Banerjee A, Schambach F, Northrop J, et al. Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells. J Exp Med. 2007;204:2015-21 pubmed
    ..T-bet, thus, appears to function as a molecular switch between central- and effector-memory cell differentiation. Antagonism of T-bet may, therefore, represent a novel strategy to offset dysfunctional programming of memory CD8+ T cells. ..
  48. Demay F, Bilican B, Rodriguez M, Carreira S, Pontecorvi M, Ling Y, et al. T-box factors: targeting to chromatin and interaction with the histone H3 N-terminal tail. Pigment Cell Res. 2007;20:279-87 pubmed
    ..Taken together our results suggest that Tbx2, and most likely other members of the T-box family, are able to target chromatin and may indicate a role for the T-box factors in epigenetic reprogramming events. ..
  49. Arnold S, Hofmann U, Bikoff E, Robertson E. Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse. Development. 2008;135:501-11 pubmed publisher
    ..Collectively, our experiments establish that Eomes is a key regulator of anteroposterior axis formation, EMT and definitive endoderm specification in the mouse. ..
  50. Liu W, Jiang X, Zhang Z. Expression of PSCA, PIWIL1, and TBX2 in endometrial adenocarcinoma. Onkologie. 2010;33:241-5 pubmed publisher
    ..Our findings suggest that PSCA and TBX2 might be candidate targets for cancer therapy, and have helped us further understand the carcinogenesis of endometrial cancer. ..
  51. Madia F, Frisullo G, Nociti V, Conte A, Luigetti M, Del Grande A, et al. pSTAT1, pSTAT3, and T-bet as markers of disease activity in chronic inflammatory demyelinating polyradiculoneuropathy. J Peripher Nerv Syst. 2009;14:107-17 pubmed publisher
    ..0073). IL10 levels were higher in active phase patients than in controls (p = 0.0334). Our data suggest that pSTAT1, T-bet, and pSTAT3 can be considered putative markers of disease activity and potential targets for specific therapies...
  52. French C, Erickson T, French D, Pilgrim D, Waskiewicz A. Gdf6a is required for the initiation of dorsal-ventral retinal patterning and lens development. Dev Biol. 2009;333:37-47 pubmed publisher
    ..Taken together, these data indicate that Gdf6a initiates dorsal retinal patterning independent of Bmp4, and regulates lens differentiation. ..
  53. Horton A, Mahadevan N, Minguillon C, Osoegawa K, Rokhsar D, Ruvinsky I, et al. Conservation of linkage and evolution of developmental function within the Tbx2/3/4/5 subfamily of T-box genes: implications for the origin of vertebrate limbs. Dev Genes Evol. 2008;218:613-28 pubmed publisher