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Gene Review

Tbx5  -  T-box 5

Mus musculus

Synonyms: T-box protein 5, T-box transcription factor TBX5
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Disease relevance of Tbx5


High impact information on Tbx5

  • In chick, ectopic expression of either Vax leads to ventralization of the early retina, as assayed by expression of the transcription factors Pax2 and Tbx5, and the Eph family members EphB2, EphB3, ephrinB1, and ephrinB2, all of which are normally dorsally or ventrally restricted [4].
  • This process is under the control of specific transcription factors such as Tbx5 and dHAND [5].
  • Mice carrying a Tbx5 null allele (Tbx5(+/Delta)) have malformations in digits, wrists, and sternum joints, regions where Tbx5 is expressed [6].
  • Tbx5 is dispensable for forelimb outgrowth [7].
  • Here we show that Tbx5 is expressed throughout the limb mesenchyme in progenitors of cartilage, tendon and muscle [7].

Biological context of Tbx5

  • Tbx5 directly activates the Fgf10 gene via a conserved binding site, providing a simple and direct mechanism for limb bud initiation [8].
  • 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 [9].
  • In mice, all of these genes have expression patterns indicative of involvement in embryonic induction (Chapman et al. (1996) Dev. Dyn., in press), and four (Tbx2-Tbx5) are represented as two cognate, linked gene pairs (Agulnik et al., (1996), Genetics, in press) [10].
  • Our study supports the idea that SRF embryonic cardiac gene expression is dependent upon the SRF 3'-UTR enhancer, Tbx2, Tbx5, and TIP60 histone acetyltransferase activity [11].
  • Myocardial cell proliferation, which has been shown previously to be suppressed by Tbx5, was also decreased in the knockout mice and rescued by the transgene [12].

Anatomical context of Tbx5

  • Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo [8].
  • Tbx5 is not essential for an early establishment of forelimb versus hindlimb identity [8].
  • We report that mouse embryos lacking Tbx5 do not form forelimb buds, although the patterning of the lateral plate mesoderm into the limb field is intact [8].
  • We find that Tbx5 is expressed throughout the central conduction system, including the atrioventricular bundle and bundle branch conduction system [13].
  • Deficiencies in the gap junction protein gene connexin 40 (Cx40), a downstream target of Tbx5, did not account for morphologic conduction system defects in Tbx5(del/+) mice [13].

Associations of Tbx5 with chemical compounds


Other interactions of Tbx5

  • We found that, whereas bud regions expressing Tbx4 developed characteristic leg structures, regions expressing Tbx5 developed characteristic wing features [14].
  • We conclude that Tbx5 is required for Cx40-independent patterning of the cardiac conduction system, and suggest that the electrophysiologic defects in Holt-Oram syndrome reflect a developmental abnormality of the conduction system [13].
  • Our findings indicate the existence of an early phase of RA signaling acting upstream of Tbx5, Meis2, and dHand, followed by a late phase of RA signaling needed to expand AER structure fully along the distal ectoderm [15].
  • 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 [16].
  • In the ventricular conduction system, Tbx5 haploinsufficiency caused patterning defects of both the left and right ventricular bundle branches, including absence or severe abnormalities of the right bundle branch [13].

Analytical, diagnostic and therapeutic context of Tbx5


  1. p204 is required for the differentiation of P19 murine embryonal carcinoma cells to beating cardiac myocytes: its expression is activated by the cardiac Gata4, Nkx2.5, and Tbx5 proteins. Ding, B., Liu, C.J., Huang, Y., Hickey, R.P., Yu, J., Kong, W., Lengyel, P. J. Biol. Chem. (2006) [Pubmed]
  2. Tbx5 is essential for heart development. Horb, M.E., Thomsen, G.H. Development (1999) [Pubmed]
  3. Microarray analysis of Tbx5-induced genes expressed in the developing heart. Plageman, T.F., Yutzey, K.E. Dev. Dyn. (2006) [Pubmed]
  4. Misexpression of the Emx-related homeobox genes cVax and mVax2 ventralizes the retina and perturbs the retinotectal map. Schulte, D., Furukawa, T., Peters, M.A., Kozak, C.A., Cepko, C.L. Neuron (1999) [Pubmed]
  5. Oriented clonal cell growth in the developing mouse myocardium underlies cardiac morphogenesis. Meilhac, S.M., Esner, M., Kerszberg, M., Moss, J.E., Buckingham, M.E. J. Cell Biol. (2004) [Pubmed]
  6. Connexin 40, a target of transcription factor Tbx5, patterns wrist, digits, and sternum. Pizard, A., Burgon, P.G., Paul, D.L., Bruneau, B.G., Seidman, C.E., Seidman, J.G. Mol. Cell. Biol. (2005) [Pubmed]
  7. Tbx5 is dispensable for forelimb outgrowth. Hasson, P., Del Buono, J., Logan, M.P. Development (2007) [Pubmed]
  8. Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo. Agarwal, P., Wylie, J.N., Galceran, J., Arkhitko, O., Li, C., Deng, C., Grosschedl, R., Bruneau, B.G. Development (2003) [Pubmed]
  9. 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]
  10. Evidence of a role for T-box genes in the evolution of limb morphogenesis and the specification of forelimb/hindlimb identity. Gibson-Brown, J.J., Agulnik, S.I., Chapman, D.L., Alexiou, M., Garvey, N., Silver, L.M., Papaioannou, V.E. Mech. Dev. (1996) [Pubmed]
  11. Serum response factor, an enriched cardiac mesoderm obligatory factor, is a downstream gene target for Tbx genes. Barron, M.R., Belaguli, N.S., Zhang, S.X., Trinh, M., Iyer, D., Merlo, X., Lough, J.W., Parmacek, M.S., Bruneau, B.G., Schwartz, R.J. J. Biol. Chem. (2005) [Pubmed]
  12. CHF1/Hey2 plays a pivotal role in left ventricular maturation through suppression of ectopic atrial gene expression. Koibuchi, N., Chin, M.T. Circ. Res. (2007) [Pubmed]
  13. The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system. Moskowitz, I.P., Pizard, A., Patel, V.V., Bruneau, B.G., Kim, J.B., Kupershmidt, S., Roden, D., Berul, C.I., Seidman, C.E., Seidman, J.G. Development (2004) [Pubmed]
  14. Involvement of T-box genes Tbx2-Tbx5 in vertebrate limb specification and development. Gibson-Brown, J.J., Agulnik, S.I., Silver, L.M., Niswander, L., Papaioannou, V.E. Development (1998) [Pubmed]
  15. Retinoic acid synthesis controlled by Raldh2 is required early for limb bud initiation and then later as a proximodistal signal during apical ectodermal ridge formation. Mic, F.A., Sirbu, I.O., Duester, G. J. Biol. Chem. (2004) [Pubmed]
  16. 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]
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