The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Tbx1  -  T-box 1

Mus musculus

Synonyms: T-box protein 1, T-box transcription factor TBX1, Testis-specific T-box protein
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Tbx1

  • Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage [1].
  • While no abnormalities in branchiomeric myogenesis were detected in Tbx1(+/-) mice, reduced TBX1 levels may contribute to pharyngeal hypotonia in del22q11.2 patients [2].
  • Mice heterozygous for a null mutation in Tbx1 have mild anomalies, whereas homozygous Tbx1 mutants die at birth with severe defects in the derivatives of the pharyngeal apparatus, including cleft palate, thymus gland aplasia and cardiac outflow tract malformations [3].
  • Thyroid dysgenesis related to Tbx1 inactivation may explain an overrepresentation of hypothyroidism occurring in patients with the 22q11DS [4].
  • Tbx1 was also inactivated in the otic vesicle (OV), resulting in the failure of inner ear sensory organ formation, and in duplication of the cochleovestibular ganglion (CVG) [5].

High impact information on Tbx1


Biological context of Tbx1

  • To dissect the epistatic relationships of these genes during embryonic development and the molecular pathogenesis of the Tbx1 mutant phenotype, we generated Fgf10+/-;Tbx1+/- and Fgf3-/-;Tbx1+/- mice [9].
  • The del22q11.2 candidate gene Tbx1 regulates branchiomeric myogenesis [2].
  • Mice hemizygous for a null allele of Tbx1 had mild malformations, while homozygotes had severe malformations in the affected structures; neither precisely modeling the syndrome [1].
  • Tbx1 therefore regulates the onset of branchiomeric myogenesis and controls normal mandibular arch development, including robust transcriptional activation of myogenic determination genes [2].
  • Our data provide the first evidence of a genetic link between Tbx1 and FGF signaling, and the first example of a modifier of the Tbx1 haploinsufficiency phenotype [10].

Anatomical context of Tbx1

  • Tbx1 is expressed in pharyngeal mesoderm, which gives rise to branchiomeric skeletal muscles of the head and neck [2].
  • Tbx1 haploinsufficiency causes aortic arch abnormalities in mice because of early growth and remodeling defects of the fourth pharyngeal arch arteries [10].
  • The function of Tbx1 in the development of these arteries is probably cell non-autonomous, as the gene is not expressed in structural components of the artery but in the surrounding pharyngeal endoderm [10].
  • We also show that Tbx1 expression is required in cells expressing Nkx2.5 for the formation of the aorto-pulmonary septum, which divides the aorta from the main pulmonary artery [11].
  • Furthermore, Shh was sufficient to induce Tbx1 expression when misexpressed in selected regions of chick embryos [12].

Associations of Tbx1 with chemical compounds

  • Cyp26a1, a gene required for retinoic acid (RA) inactivation during embryogenesis, was previously identified as a potential Tbx1 target from a microarray screen comparing wild-type and null Tbx1 mouse embryo pharyngeal arches (pa) at E9 [13].
  • Down-regulation of Tbx1 itself was observed, in accordance with previous observations that RA represses Tbx1 expression [13].
  • In vitamin A-deficient quails, which lack endogenous retinoic acid, Tbx1 expression patterns were disrupted early in development and expression was subsequently lost in all tissues. "Gain-of-function" experiments where RA-soaked beads were grafted into the pharyngeal region produced localized down-regulation of Tbx1 expression [14].
  • Tbx6 is a member of the T-box family of proteins, which share a region of homology corresponding to the DNA-binding domain of the transcription factor T [15].
  • T-box genes encode putative transcription factors implicated in diverse developmental processes (Papaioannou, V.E. and Silver, L.M., 1998. BioEssays 20, 9-19) [16].

Physical interactions of Tbx1

  • In vivo inactivation of a T-box factor (TBE)- or NK2-homeobox factor binding element (NKE) within the ANF fragment removed the repression in the AVC without affecting its chamber activity [17].
  • In one of these genes, T-box binding protein-2 (Tbx-2), an RA response element, was identified in the promoter region that mediates the RA responsiveness of this gene [18].

Regulatory relationships of Tbx1

  • These studies reveal a Shh-mediated pathway that regulates Tbx1 during pharyngeal arch development [12].
  • Our data present a paradigm by which T-box proteins regulate regional differences in Nmyc1 expression and proliferation to effect organ morphogenesis [19].
  • Tbt-1, a new T-box transcription factor induced in activated Th1 and CD8+ T cells [20].
  • The T-box expressed in T cells gene (T-bet) is a member of the T-box family of transcription factors [21].
  • Itk(-/-) and Rlk(-/-)Itk(-/-) CD8(+) thymocytes expressed abundant transcripts for the T box transcription factor, eomesodermin, correlating with their phenotype and function [22].

Other interactions of Tbx1

  • We found that Fgf8 mutation increases the severity of the primary defect caused by Tbx1 haploinsufficiency, i.e. early hypoplasia of the fourth pharyngeal arch arteries, consistent with the time and location of the shared expression domain of the two genes [10].
  • This is a clear reflection of the evolutionary relationship between the 5 genes since the divergence of Tbx1 occurred long before the relatively recent divergence of Tbx2 and 3 and Tbx4 and 5 from common ancestral genes [23].
  • As the basis for further study of the function and evolution of these genes, we have examined the expression of 5 of these genes, Tbx1-Tbx5, across a wide range of embryonic stages from blastocyst through gastrulation and early organogenesis by in situ hybridization of wholemounts and tissue sections [23].
  • A genetic link between Tbx1 and fibroblast growth factor signaling [10].
  • We found that Tbx1 expression was dependent upon Shh signaling in mouse embryos, consistent with their overlapping expression in the pharyngeal arches [12].

Analytical, diagnostic and therapeutic context of Tbx1


  1. Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage. Liao, J., Kochilas, L., Nowotschin, S., Arnold, J.S., Aggarwal, V.S., Epstein, J.A., Brown, M.C., Adams, J., Morrow, B.E. Hum. Mol. Genet. (2004) [Pubmed]
  2. The del22q11.2 candidate gene Tbx1 regulates branchiomeric myogenesis. Kelly, R.G., Jerome-Majewska, L.A., Papaioannou, V.E. Hum. Mol. Genet. (2004) [Pubmed]
  3. Inactivation of Tbx1 in the pharyngeal endoderm results in 22q11DS malformations. Arnold, J.S., Werling, U., Braunstein, E.M., Liao, J., Nowotschin, S., Edelmann, W., Hebert, J.M., Morrow, B.E. Development (2006) [Pubmed]
  4. The 22q11 deletion syndrome candidate gene Tbx1 determines thyroid size and positioning. Fagman, H., Liao, J., Westerlund, J., Andersson, L., Morrow, B.E., Nilsson, M. Hum. Mol. Genet. (2007) [Pubmed]
  5. Tissue-specific roles of Tbx1 in the development of the outer, middle and inner ear, defective in 22q11DS patients. Arnold, J.S., Braunstein, E.M., Ohyama, T., Groves, A.K., Adams, J.C., Brown, M.C., Morrow, B.E. Hum. Mol. Genet. (2006) [Pubmed]
  6. Tbx24, encoding a T-box protein, is mutated in the zebrafish somite-segmentation mutant fused somites. Nikaido, M., Kawakami, A., Sawada, A., Furutani-Seiki, M., Takeda, H., Araki, K. Nat. Genet. (2002) [Pubmed]
  7. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Jerome, L.A., Papaioannou, V.E. Nat. Genet. (2001) [Pubmed]
  8. An ancient family of embryonically expressed mouse genes sharing a conserved protein motif with the T locus. Bollag, R.J., Siegfried, Z., Cebra-Thomas, J.A., Garvey, N., Davison, E.M., Silver, L.M. Nat. Genet. (1994) [Pubmed]
  9. Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests functional redundancy. Aggarwal, V.S., Liao, J., Bondarev, A., Schimmang, T., Lewandoski, M., Locker, J., Shanske, A., Campione, M., Morrow, B.E. Hum. Mol. Genet. (2006) [Pubmed]
  10. A genetic link between Tbx1 and fibroblast growth factor signaling. Vitelli, F., Taddei, I., Morishima, M., Meyers, E.N., Lindsay, E.A., Baldini, A. Development (2002) [Pubmed]
  11. Tbx1 has a dual role in the morphogenesis of the cardiac outflow tract. Xu, H., Morishima, M., Wylie, J.N., Schwartz, R.J., Bruneau, B.G., Lindsay, E.A., Baldini, A. Development (2004) [Pubmed]
  12. Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development. Garg, V., Yamagishi, C., Hu, T., Kathiriya, I.S., Yamagishi, H., Srivastava, D. Dev. Biol. (2001) [Pubmed]
  13. 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. Roberts, C., Ivins, S., Cook, A.C., Baldini, A., Scambler, P.J. Hum. Mol. Genet. (2006) [Pubmed]
  14. Retinoic acid down-regulates Tbx1 expression in vivo and in vitro. Roberts, C., Ivins, S.M., James, C.T., Scambler, P.J. Dev. Dyn. (2005) [Pubmed]
  15. The human TBX6 gene: cloning and assignment to chromosome 16p11.2. Papapetrou, C., Putt, W., Fox, M., Edwards, Y.H. Genomics (1999) [Pubmed]
  16. Expression of T-box genes Tbx2-Tbx5 during chick organogenesis. Gibson-Brown, J.J., I Agulnik S, n.u.l.l., Silver, L.M., Papaioannou, V.E. Mech. Dev. (1998) [Pubmed]
  17. Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation. Habets, P.E., Moorman, A.F., Clout, D.E., van Roon, M.A., Lingbeek, M., van Lohuizen, M., Campione, M., Christoffels, V.M. Genes Dev. (2002) [Pubmed]
  18. Vitamin A (retinoids) regulation of mouse melanoma growth and differentiation. Niles, R.M. J. Nutr. (2003) [Pubmed]
  19. T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis. Cai, C.L., Zhou, W., Yang, L., Bu, L., Qyang, Y., Zhang, X., Li, X., Rosenfeld, M.G., Chen, J., Evans, S. Development (2005) [Pubmed]
  20. Tbt-1, a new T-box transcription factor induced in activated Th1 and CD8+ T cells. Shier, P., Hofstra, C.L., Ma, X.J., Wu, Y., Ngo, K., Fung-Leung, W.P. Immunogenetics (2000) [Pubmed]
  21. Absence of the T-bet gene coding for the Th1-related transcription factor does not affect diabetes-associated phenotypes in Balb/c mice. Melanitou, E., Liu, E., Miao, D., Yu, L., Glimcher, L.H., Eisenbarth, G. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  22. The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells. Atherly, L.O., Lucas, J.A., Felices, M., Yin, C.C., Reiner, S.L., Berg, L.J. Immunity (2006) [Pubmed]
  23. Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. Chapman, D.L., Garvey, N., Hancock, S., Alexiou, M., Agulnik, S.I., Gibson-Brown, J.J., Cebra-Thomas, J., Bollag, R.J., Silver, L.M., Papaioannou, V.E. Dev. Dyn. (1996) [Pubmed]
  24. Tbx1 affects asymmetric cardiac morphogenesis by regulating Pitx2 in the secondary heart field. Nowotschin, S., Liao, J., Gage, P.J., Epstein, J.A., Campione, M., Morrow, B.E. Development (2006) [Pubmed]
  25. Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1. Ivins, S., Lammerts van Beuren, K., Roberts, C., James, C., Lindsay, E., Baldini, A., Ataliotis, P., Scambler, P.J. Dev. Biol. (2005) [Pubmed]
  26. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Lindsay, E.A., Vitelli, F., Su, H., Morishima, M., Huynh, T., Pramparo, T., Jurecic, V., Ogunrinu, G., Sutherland, H.F., Scambler, P.J., Bradley, A., Baldini, A. Nature (2001) [Pubmed]
WikiGenes - Universities