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Gene Review

Tbx3  -  T-box 3

Mus musculus

Synonyms: D5Ertd189e, T-box protein 3, T-box transcription factor TBX3
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High impact information on Tbx3

  • Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome [1].
  • Tbx-2 and Tbx-3 are expressed in anterior and posterior domains in wings and legs, as well as throughout the flank [2].
  • We show that expression of Tbx3 together with Myc or oncogenic Ras (H-Ras(Val17)) leads to efficient transformation of mouse embryo fibroblasts [3].
  • Mutations in Tbx3 cause ulnar-mammary syndrome, an autosomal dominant disorder characterized by upper limb defects, apocrine-gland defects including mammary hypoplasia, and tooth, hair and genital defects [3].
  • Here we carried out tissue transplantations, grafted beads soaked in Shh, Bmps, and Noggin in chick limb buds, and analysed Tbx3 expression [4].

Biological context of Tbx3

  • Our analysis implicates a role for Tbx3 in repressing a chamber-specific program of gene expression in regions from which the components of the central conduction system are subsequently formed [5].
  • Blocking Tbx3 expression by small interfering RNA decreased cell number and [(3)H]Thymidine incorporation (P < 0.01) [6].
  • In spite of a large body of evidence implicating these genes in cell cycle control through the p19(Arf)/p53 pathways, we find no evidence for involvement of these pathways either in embryonic lethality of homozygous mutants or in the mammary gland phenotype of Tbx3 heterozygous mice [7].
  • However, the deficiency in maintenance of the mammary placodes in Tbx2, Tbx3 double heterozygous mice is more marked than in Tbx3 single heterozygotes, indicating a genetic interaction between the two genes [7].
  • The harmonization between Tbx3 and Bmp4 therefore controls cell proliferation to regulate secondary palate development [8].

Anatomical context of Tbx3

  • Throughout cardiac development, Tbx3 is expressed in an uninterrupted myocardial domain that extends from the sinoatrial node to the atrioventricular region [5].
  • Tbx3 is expressed earliest, in the inner cell mass of the blastocyst [9].
  • In several cases there is complementary expression of different genes in 2 interacting tissues, as in the lung epithelium (Tbx1) and lung mesenchyme (Tbx2-5), and in mammary buds (Tbx3) and mammary stroma (Tbx2) [9].
  • Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos [10].
  • Anterior Tbx3 expression appears to be related to the width of limb bud, which determines digit number [4].

Associations of Tbx3 with chemical compounds

  • We also investigated Tbx3 expression in limb buds of chicken and mouse mutants and retinoid-deficient quail in which anteroposterior patterning is abnormal [4].

Regulatory relationships of Tbx3


Other interactions of Tbx3

  • Tbx3 expression increased during osteoblast differentiation and following BMP-7 and Wnt3a treatment (P </= 0.05) [6].
  • Tbx3 expression is reported to be associated with Bmp4 signaling during the process of organogenesis in other areas, such as limb development [8].

Analytical, diagnostic and therapeutic context of Tbx3


  1. Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Davenport, T.G., Jerome-Majewska, L.A., Papaioannou, V.E. Development (2003) [Pubmed]
  2. Tbx genes and limb identity in chick embryo development. Isaac, A., Rodriguez-Esteban, C., Ryan, A., Altabef, M., Tsukui, T., Patel, K., Tickle, C., Izpisúa-Belmonte, J.C. Development (1998) [Pubmed]
  3. Tbx3 impinges on the p53 pathway to suppress apoptosis, facilitate cell transformation and block myogenic differentiation. Carlson, H., Ota, S., Song, Y., Chen, Y., Hurlin, P.J. Oncogene (2002) [Pubmed]
  4. Regulation of Tbx3 expression by anteroposterior signalling in vertebrate limb development. Tümpel, S., Sanz-Ezquerro, J.J., Isaac, A., Eblaghie, M.C., Dobson, J., Tickle, C. Dev. Biol. (2002) [Pubmed]
  5. The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. Hoogaars, W.M., Tessari, A., Moorman, A.F., de Boer, P.A., Hagoort, J., Soufan, A.T., Campione, M., Christoffels, V.M. Cardiovasc. Res. (2004) [Pubmed]
  6. Whole genome microarray analysis of growth hormone-induced gene expression in bone: T-box3, a novel transcription factor, regulates osteoblast proliferation. Govoni, K.E., Lee, S.K., Chadwick, R.B., Yu, H., Kasukawa, Y., Baylink, D.J., Mohan, S. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  7. Tbx3, the ulnar-mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53-independent pathway. Jerome-Majewska, L.A., Jenkins, G.P., Ernstoff, E., Zindy, F., Sherr, C.J., Papaioannou, V.E. Dev. Dyn. (2005) [Pubmed]
  8. Modulation of cell proliferation during palatogenesis by the interplay between Tbx3 and Bmp4. Lee, J.M., Kim, J.Y., Cho, K.W., Lee, M.J., Cho, S.W., Zhang, Y., Byun, S.K., Yi, C.K., Jung, H.S. Cell Tissue Res. (2007) [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. Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos. Eblaghie, M.C., Song, S.J., Kim, J.Y., Akita, K., Tickle, C., Jung, H.S. J. Anat. (2004) [Pubmed]
  11. Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development. Cho, K.W., Kim, J.Y., Song, S.J., Farrell, E., Eblaghie, M.C., Kim, H.J., Tickle, C., Jung, H.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
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