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Gene Review

T  -  brachyury

Mus musculus

Synonyms: Bra, Brachyury protein, D17Mit170, Low, Lr, ...
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Disease relevance of T

  • CONCLUSION: Low intravenous doses of FGF1 or FGF2 appear to protect bone marrow from the toxic effects of radiation without increasing the rates of tumor growth or metastases or decreasing the radiosensitivity of tumors [1].
  • Expression of the Brachyury gene during mesoderm development in differentiating embryonal carcinoma cell cultures [2].
  • We demonstrate that hypoxia accelerates the expression of Brachyury (a mesoderm-specific transcription factor), BMP4 (a mesoderm-promoting growth factor) and FLK1 (a marker of hemangioblasts, the bipotential progenitor of endothelial and hematopoietic cells) in differentiating ES cell cultures [3].
  • Using the inhibitor of de novo pyrimidine biosynthesis, phosphonoacetyl-L-aspartate (PALA), as selective agent we found that PALA resistant cells arise with a frequency of about 5 x 10(-5) and that the interaction of polyomavirus large T protein with the retinoblastoma protein or another related pocket protein is important for this to occur [4].
  • Association between historically high frequencies of neural tube defects and the human T homologue of mouse T (Brachyury) [5].

Psychiatry related information on T

  • BACKGROUND: Low doses of the N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 (dizocilpine) or ethanol increase locomotor activity to a lesser extent in long-sleep (LS), than in short-sleep (SS), mice [6].
  • RESULTS: Low doses and high doses of celecoxib significantly lengthened the tumor latency period (P<.03 and P<.003, respectively) and reduced tumor multiplicity (P<.005 and P<.001, respectively) compared with controls [7].
  • BACKGROUND: Low-dose ethanol-induced activation (LDA) and initial sensitivity to alcohol are both predictors of alcohol abuse in human populations [8].
  • We have also developed replicate lines of mice selectively bred for high (High Exploratory Behavior: HEB) or low (Low Exploratory Behavior: LEB) head dipping on a hole-board and evaluated the effects of diazepam and methamphetamine on hole-board behaviors in these mice [9].

High impact information on T


Chemical compound and disease context of T


Biological context of T


Anatomical context of T

  • They consist of misfolded ectodermal and endodermal cell layers, do not form a primitive streak or any detectable mesodermal cells and fail to express the developmental marker genes Bra (T), Bmp-2/4 and Shh [24].
  • Brachyury is required for elongation and vasculogenesis in the murine allantois [25].
  • Within the caudal notochord, developing floorplate, and hindgut, HNF3alpha, HNF3beta, Shh, and Brachyury expression domains correlate directly with known genetic roles and predicted tissue interdependence during induction and differentiation of these structures [26].
  • Brachyury homozygotes fail to make posterior somites, notochord, floor plate, and a placental connection, resulting in death by 10.5 days of development [27].
  • In embryos dissected between 5.5 and 6.5 dpc, Brachyury is first expressed in the distal extra-embryonic ectoderm and subsequently on one side of the epiblast [28].

Associations of T with chemical compounds


Physical interactions of T

  • Isoforms with an intact T-box bound specifically to DNA sites resembling the consensus brachyury half site, although with less avidity compared with the related factor, Tbx5 [33].
  • Mga binds the preferred Brachyury-binding sequence and represses transcription of reporter genes containing promoter-proximal Brachyury-binding sites [34].

Regulatory relationships of T

  • Here we show that Brachyury is specifically down-regulated in Wnt3a mutants in cells fated to form paraxial mesoderm [35].
  • Reduction of MACF1 in Wnt-1-expressing P19 cells resulted in decreased T (Brachyury) gene expression, a DNA-binding transcription factor that is a direct target of Wnt/beta-catenin signaling and required for mesoderm formation [36].
  • The presence (or absence) of E-cadherin regulates the expression of the transcription factor T-brachyury, indicating that cadherins play a role in linking cell surface receptors and gene expression [37].
  • ES cells thus deprived of LIF/DIA differentiate spontaneously to a cell type that expresses Brachyury (T), a marker of early mesoderm [38].
  • Here, we show that Nanog expression is up-regulated in mouse ES cells by the binding of T (Brachyury) and STAT3 to an enhancer element in the mouse Nanog gene [39].

Other interactions of T

  • T1, T2, and the unlinked t-int are distinct and unrelated loci, and mutations in these genes do not complement one another genetically [40].
  • An allele of the mouse brachyury locus, T22H, had been shown previously to involve a deletion of several markers in the proximal part of chromosome 17, and almost certainly includes deletion of the t-complex distorter gene Tcd-1 [41].
  • We have compared the expression pattern of myogenic markers and markers for the hypaxial muscle precursors in the mutants Brachyury curtailed, truncate, Danforth's short tail and Pintail [42].
  • In vitro, DNA binding studies show that it binds to the GC box, a DNA motif present in the promoter of a very large number of genes, including Brachyury, and recognised by members of the Sp1 family [19].
  • T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification [35].

Analytical, diagnostic and therapeutic context of T

  • The existence of a second gene mapping near Brachyury and affecting the same developmental processes was alluded to over 50 years ago and has been debated ever since [27].
  • Whole mount in situ hybridization of Pax6 revealed a normal pattern while staining by sonic hedgehog (shh) and Brachyury (T) exhibited abnormal patterns in the anterior-posterior (A-P) direction at both mesencephalic and thoracic levels [43].
  • (1) A cDNA fragment encoding 212 amino acids of the rabbit Brachyury gene was cloned by RT-PCR and used as a molecular marker for mesoderm progenitors [44].
  • CONCLUSION: Low-dose radiosensitization of actively dividing tumor cells by PARP-1 inhibitors suggests that they may have a role in enhancing the efficacy of ultrafractionated or low-dose-rate radiotherapy regimens [45].
  • CONCLUSIONS: Low AR expression and maintained stroma IGF-1 synthesis may result in limited tumor cell death after castration therapy [46].


  1. Tumor growth and tumor radiosensitivity in mice given myeloprotective doses of fibroblast growth factors. Ding, I., Huang, K., Snyder, M.L., Cook, J., Zhang, L., Wersto, N., Okunieff, P. J. Natl. Cancer Inst. (1996) [Pubmed]
  2. Expression of the Brachyury gene during mesoderm development in differentiating embryonal carcinoma cell cultures. Vidricaire, G., Jardine, K., McBurney, M.W. Development (1994) [Pubmed]
  3. Hypoxia affects mesoderm and enhances hemangioblast specification during early development. Ramírez-Bergeron, D.L., Runge, A., Dahl, K.D., Fehling, H.J., Keller, G., Simon, M.C. Development (2004) [Pubmed]
  4. Polyomavirus large T antigen-dependent DNA amplification. Stiegler, P., Schüchner, S., Lestou, V., Wintersberger, E. Oncogene (1997) [Pubmed]
  5. Association between historically high frequencies of neural tube defects and the human T homologue of mouse T (Brachyury). Shields, D.C., Ramsbottom, D., Donoghue, C., Pinjon, E., Kirke, P.N., Molloy, A.M., Edwards, Y.H., Mills, J.L., Mynett-Johnson, L., Weir, D.G., Scott, J.M., Whitehead, A.S. Am. J. Med. Genet. (2000) [Pubmed]
  6. MK-801-induced locomotor activity in long-sleep x short-sleep recombinant inbred mouse strains: correlational analysis with low-dose ethanol and provisional quantitative trait loci. Zahniser, N.R., Negri, C.A., Hanania, T., Gehle, V.M. Alcohol. Clin. Exp. Res. (1999) [Pubmed]
  7. Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer: a study in the hairless mouse model. Orengo, I.F., Gerguis, J., Phillips, R., Guevara, A., Lewis, A.T., Black, H.S. Archives of dermatology. (2002) [Pubmed]
  8. Evidence that the Lore-1 region specifies ethanol-induced activation in addition to sedative/hypnotic sensitivity to ethanol. Owens, J.C., Bennett, B., Johnson, T.E. Alcohol. Clin. Exp. Res. (2001) [Pubmed]
  9. Pharmacological and genetic influences on hole-board behaviors in mice. Kliethermes, C.L., Crabbe, J.C. Pharmacol. Biochem. Behav. (2006) [Pubmed]
  10. Transmeiotic differentiation of male germ cells in culture. Rassoulzadegan, M., Paquis-Flucklinger, V., Bertino, B., Sage, J., Jasin, M., Miyagawa, K., van Heyningen, V., Besmer, P., Cuzin, F. Cell (1993) [Pubmed]
  11. Expression of a Xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction. Smith, J.C., Price, B.M., Green, J.B., Weigel, D., Herrmann, B.G. Cell (1991) [Pubmed]
  12. Endothelial cell tumors develop in transgenic mice carrying polyoma virus middle T oncogene. Bautch, V.L., Toda, S., Hassell, J.A., Hanahan, D. Cell (1987) [Pubmed]
  13. Germ line transmission of autonomous genetic elements in transgenic mouse strains. Rassoulzadegan, M., Léopold, P., Vailly, J., Cuzin, F. Cell (1986) [Pubmed]
  14. Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice. Verschuren, L., Kleemann, R., Offerman, E.H., Szalai, A.J., Emeis, S.J., Princen, H.M., Kooistra, T. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  15. Genetically based resistance to the antiinflammatory effects of methotrexate in the air-pouch model of acute inflammation. Delano, D.L., Montesinos, M.C., Desai, A., Wilder, T., Fernandez, P., D'Eustachio, P., Wiltshire, T., Cronstein, B.N. Arthritis Rheum. (2005) [Pubmed]
  16. Molecular cloning, chromosomal organization, and functional characterization of a sodium-dicarboxylate cotransporter from mouse kidney. Pajor, A.M., Sun, N.N. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  17. Low dose suramin as a chemosensitizer of bladder cancer to mitomycin C. Xin, Y., Lyness, G., Chen, D., Song, S., Wientjes, M.G., Au, J.L. J. Urol. (2005) [Pubmed]
  18. Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes. Lolmède, K., Durand de Saint Front, V., Galitzky, J., Lafontan, M., Bouloumié, A. Int. J. Obes. Relat. Metab. Disord. (2003) [Pubmed]
  19. Sp5, a new member of the Sp1 family, is dynamically expressed during development and genetically interacts with Brachyury. Harrison, S.M., Houzelstein, D., Dunwoodie, S.L., Beddington, R.S. Dev. Biol. (2000) [Pubmed]
  20. Genetic analysis of mouse t haplotypes using mutations induced by ethylnitrosourea mutagenesis: the order of T and qk is inverted in t mutants. Justice, M.J., Bode, V.C. Genetics (1988) [Pubmed]
  21. Expression of the novel murine homeobox gene Sax-1 in the developing nervous system. Schubert, F.R., Fainsod, A., Gruenbaum, Y., Gruss, P. Mech. Dev. (1995) [Pubmed]
  22. A novel partial t haplotype with a brachyury-independent effect on tail phenotype. Fujimoto, A., Wakasugi, N., Tomita, T. Mamm. Genome (1995) [Pubmed]
  23. Alterations in gene expression during mesoderm formation and axial patterning in Brachyury (T) embryos. Rashbass, P., Wilson, V., Rosen, B., Beddington, R.S. Int. J. Dev. Biol. (1994) [Pubmed]
  24. Serum response factor is essential for mesoderm formation during mouse embryogenesis. Arsenian, S., Weinhold, B., Oelgeschläger, M., Rüther, U., Nordheim, A. EMBO J. (1998) [Pubmed]
  25. Brachyury is required for elongation and vasculogenesis in the murine allantois. Inman, K.E., Downs, K.M. Development (2006) [Pubmed]
  26. Genetic patterning of the developing mouse tail at the time of posterior neuropore closure. Gofflot, F., Hall, M., Morriss-Kay, G.M. Dev. Dyn. (1997) [Pubmed]
  27. Is there a Brachyury the Second? Analysis of a transgenic mutation involved in notochord maintenance in mice. Rennebeck, G.M., Lader, E., Chen, Q., Bohm, R.A., Cai, Z.S., Faust, C., Magnuson, T., Pease, L.R., Artzt, K. Dev. Biol. (1995) [Pubmed]
  28. Primitive streak formation in mice is preceded by localized activation of Brachyury and Wnt3. Rivera-Pérez, J.A., Magnuson, T. Dev. Biol. (2005) [Pubmed]
  29. BMP Stimulation of Alkaline Phosphatase Activity in Pluripotent Mouse C2C12 Cells is Inhibited by Dermatopontin, One of the Most Abundant Low Molecular Weight Proteins in Demineralized Bone Matrix. Behnam, K., Murray, S.S., Brochmann, E.J. Connect. Tissue Res. (2006) [Pubmed]
  30. Immortalization of human adult normal prostatic epithelial cells by liposomes containing large T-SV40 gene. Cussenot, O., Berthon, P., Berger, R., Mowszowicz, I., Faille, A., Hojman, F., Teillac, P., Le Duc, A., Calvo, F. J. Urol. (1991) [Pubmed]
  31. Retinoic acid promotes neural and represses mesodermal gene expression in mouse embryonic stem cells in culture. Bain, G., Ray, W.J., Yao, M., Gottlieb, D.I. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  32. In vitro maturation of ovine oocytes in a portable incubator. Byrd, S.R., Flores-Foxworth, G., Applewhite, A.A., Westhusin, M.E. Theriogenology (1997) [Pubmed]
  33. Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Stennard, F.A., Costa, M.W., Elliott, D.A., Rankin, S., Haast, S.J., Lai, D., McDonald, L.P., Niederreither, K., Dolle, P., Bruneau, B.G., Zorn, A.M., Harvey, R.P. Dev. Biol. (2003) [Pubmed]
  34. Mga, a dual-specificity transcription factor that interacts with Max and contains a T-domain DNA-binding motif. Hurlin, P.J., Steingrìmsson, E., Copeland, N.G., Jenkins, N.A., Eisenman, R.N. EMBO J. (1999) [Pubmed]
  35. T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification. Yamaguchi, T.P., Takada, S., Yoshikawa, Y., Wu, N., McMahon, A.P. Genes Dev. (1999) [Pubmed]
  36. The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway. Chen, H.J., Lin, C.M., Lin, C.S., Perez-Olle, R., Leung, C.L., Liem, R.K. Genes Dev. (2006) [Pubmed]
  37. A role for cadherins in tissue formation. Larue, L., Antos, C., Butz, S., Huber, O., Delmas, V., Dominis, M., Kemler, R. Development (1996) [Pubmed]
  38. Secretion of transforming growth factor-beta isoforms by embryonic stem cells: isoform and latency are dependent on direction of differentiation. Slager, H.G., Freund, E., Buiting, A.M., Feijen, A., Mummery, C.L. J. Cell. Physiol. (1993) [Pubmed]
  39. Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells. Suzuki, A., Raya, A., Kawakami, Y., Morita, M., Matsui, T., Nakashima, K., Gage, F.H., Rodríguez-Esteban, C., Izpisúa Belmonte, J.C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  40. Mouse Brachyury the Second (T2) is a gene next to classical T and a candidate gene for tct. Rennebeck, G., Lader, E., Fujimoto, A., Lei, E.P., Artzt, K. Genetics (1998) [Pubmed]
  41. Deletion of mouse t-complex distorter-1 produces an effect like that of the t-form of the distorter. Lyon, M.F. Genet. Res. (1992) [Pubmed]
  42. The role of the notochord for epaxial myotome formation in the mouse. Dietrich, S., Schubert, F.R., Gruss, P., Lumsden, A. Cell. Mol. Biol. (Noisy-le-grand) (1999) [Pubmed]
  43. Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis. Takeda, S., Yonekawa, Y., Tanaka, Y., Okada, Y., Nonaka, S., Hirokawa, N. J. Cell Biol. (1999) [Pubmed]
  44. Low proliferative and high migratory activity in the area of Brachyury expressing mesoderm progenitor cells in the gastrulating rabbit embryo. Viebahn, C., Stortz, C., Mitchell, S.A., Blum, M. Development (2002) [Pubmed]
  45. PARP-1, PARP-2, and the cellular response to low doses of ionizing radiation. Chalmers, A., Johnston, P., Woodcock, M., Joiner, M., Marples, B. Int. J. Radiat. Oncol. Biol. Phys. (2004) [Pubmed]
  46. Castration-induced epithelial cell death in human prostate tissue is related to locally reduced IGF-1 levels. Ohlson, N., Bergh, A., Stattin, P., Wikstr??m, P. Prostate (2007) [Pubmed]
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