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Gene Review

Tbx4  -  T-box 4

Mus musculus

Synonyms: T-box protein 4, T-box transcription factor TBX4
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High impact information on Tbx4

  • On the basis of similar expression patterns in chick, targeted misexpression of chick Pitx1 in the developing wing bud causes the resulting limb to assume altered digit number and morphogenesis, with Tbx4 induction [1].
  • However, hindlimb buds from Tbx4 mutants fail to develop either in vivo or in vitro and do not maintain Fgf10 expression in the mesenchyme [2].
  • Tbx4 is a member of the T-box family of transcription factor genes, which have been shown to play important roles in development [2].
  • Loss of Tbx4 blocks hindlimb development and affects vascularization and fusion of the allantois [2].
  • We have ablated Tbx4 function using targeted mutagenesis in the mouse [2].

Biological context of Tbx4

  • These observations suggest that T-box genes have played a role in the evolution of fin and limb morphogenesis, and that Tbx5 and Tbx4 may have been divergently selected to play a role in the differential specification of fore- (pectoral) versus hind- (pelvic) limb (fin) identity [3].
  • In addition, newt and axolotl Tbx4 and Tbx5 expression is regulated differently during embryogenesis and regenerative morphogenesis [4].

Anatomical context of Tbx4


Other interactions of Tbx4

  • By using antisense oligonucleotides (AS ODNs) and in vitro culture of embryonic lungs, we demonstrate that the transcription factors Tbx4 and Tbx5 are critical for the expression of mesenchymal FGF10 [7].
  • Our results support a role for Tbx5 and Tbx4, but not for Pitx1, in initiation of limb outgrowth [6].


  1. Role of the Bicoid-related homeodomain factor Pitx1 in specifying hindlimb morphogenesis and pituitary development. Szeto, D.P., Rodriguez-Esteban, C., Ryan, A.K., O'Connell, S.M., Liu, F., Kioussi, C., Gleiberman, A.S., Izpisúa-Belmonte, J.C., Rosenfeld, M.G. Genes Dev. (1999) [Pubmed]
  2. Loss of Tbx4 blocks hindlimb development and affects vascularization and fusion of the allantois. Naiche, L.A., Papaioannou, V.E. Development (2003) [Pubmed]
  3. 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]
  4. Different regulation of T-box genes Tbx4 and Tbx5 during limb development and limb regeneration. Khan, P., Linkhart, B., Simon, H.G. Dev. Biol. (2002) [Pubmed]
  5. Requirement for fibroblast growth factor 10 or fibroblast growth factor receptor 2-IIIb signaling for cecal development in mouse. Burns, R.C., Fairbanks, T.J., Sala, F., De Langhe, S., Mailleux, A., Thiery, J.P., Dickson, C., Itoh, N., Warburton, D., Anderson, K.D., Bellusci, S. Dev. Biol. (2004) [Pubmed]
  6. Tbx5 and Tbx4 are not sufficient to determine limb-specific morphologies but have common roles in initiating limb outgrowth. Minguillon, C., Del Buono, J., Logan, M.P. Dev. Cell (2005) [Pubmed]
  7. T-box gene products are required for mesenchymal induction of epithelial branching in the embryonic mouse lung. Cebra-Thomas, J.A., Bromer, J., Gardner, R., Lam, G.K., Sheipe, H., Gilbert, S.F. Dev. Dyn. (2003) [Pubmed]
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