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Gene Review

TBX4  -  T-box 4

Homo sapiens

 
 
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High impact information on TBX4

  • Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds [1].
  • The T-box genes Tbx4 and Tbx5 regulate limb outgrowth and identity [2].
  • Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity [3].
  • Mutations in the human TBX4 gene cause small patella syndrome [4].
  • The present identification of heterozygous TBX4 mutations in SPS patients, together with the similar skeletal phenotype of animals lacking Tbx4, establish the importance of TBX4 in the developmental pathways of the lower limbs and the pelvis in humans [4].
 

Biological context of TBX4

  • A boundary of Tbx5/Tbx4 exists in all ectopic limbs, indicating that the additional limbs are essentially chimeric, although the degree of chimerism is dependent on the position [5].
 

Anatomical context of TBX4

  • Despite evidence from ectopic expression studies, our work establishes that loss of Tbx4 has no effect on hindlimb identity as assessed by morphology or molecular markers [6].
  • This additional limb formation was accompanied by the induction of both Wnt and Fgf genes These results highlight the pivotal roles of Tbx5 and Tbx4 during limb initiation, specification of forelimb/hindlimb and evolution of tetrapod limbs, placing Tbx genes at the center of a highly conserved genetic program [7].
  • By using the RT-PCR technique on chick embryos, the onset of specific Tbx5/Tbx4 expression in the wing/leg region was estimated to be stage 13 [8].
  • Level-specific role of paraxial mesoderm in regulation of Tbx5/Tbx4 expression and limb initiation [9].
 

Other interactions of TBX4

  • Virtual cloning and physical mapping of a human T-box gene, TBX4 [10].
  • TBX4, a human member of the Tbx2/3/4/5 subfamily, has been identified and characterized from a high-throughput genomic sequence [10].
  • Thus, it is thought that Tbx5 and Tbx4 might be involved in determining limb identity [1].
  • However, ablation of Tbx4 shortly after onset of expression in the hindlimb field, during limb bud formation, alters neither limb outgrowth nor expression of Fgf10 [6].
  • Since both LMX1B and TBX4 are involved in a common molecular pathway, it is likely that the causative gene of genitopatellar syndrome functions within the same developmental process [11].
 

Analytical, diagnostic and therapeutic context of TBX4

  • The genomic organization of TBX4 was elucidated by computational sequence analysis, and the putative cDNA sequence was assembled [10].

References

  1. Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds. Takeuchi, J.K., Koshiba-Takeuchi, K., Matsumoto, K., Vogel-Höpker, A., Naitoh-Matsuo, M., Ogura, K., Takahashi, N., Yasuda, K., Ogura, T. Nature (1999) [Pubmed]
  2. The T-box genes Tbx4 and Tbx5 regulate limb outgrowth and identity. Rodriguez-Esteban, C., Tsukui, T., Yonei, S., Magallon, J., Tamura, K., Izpisua Belmonte, J.C. Nature (1999) [Pubmed]
  3. Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity. Logan, M., Tabin, C.J. Science (1999) [Pubmed]
  4. Mutations in the human TBX4 gene cause small patella syndrome. Bongers, E.M., Duijf, P.H., van Beersum, S.E., Schoots, J., Van Kampen, A., Burckhardt, A., Hamel, B.C., Losan, F., Hoefsloot, L.H., Yntema, H.G., Knoers, N.V., van Bokhoven, H. Am. J. Hum. Genet. (2004) [Pubmed]
  5. Correlation of wing-leg identity in ectopic FGF-induced chimeric limbs with the differential expression of chick Tbx5 and Tbx4. Ohuchi, H., Takeuchi, J., Yoshioka, H., Ishimaru, Y., Ogura, K., Takahashi, N., Ogura, T., Noji, S. Development (1998) [Pubmed]
  6. Tbx4 is not required for hindlimb identity or post-bud hindlimb outgrowth. Naiche, L.A., Papaioannou, V.E. Development (2007) [Pubmed]
  7. Tbx5 and Tbx4 trigger limb initiation through activation of the Wnt/Fgf signaling cascade. Takeuchi, J.K., Koshiba-Takeuchi, K., Suzuki, T., Kamimura, M., Ogura, K., Ogura, T. Development (2003) [Pubmed]
  8. Specification and determination of limb identity: evidence for inhibitory regulation of Tbx gene expression. Saito, D., Yonei-Tamura, S., Kano, K., Ide, H., Tamura, K. Development (2002) [Pubmed]
  9. Level-specific role of paraxial mesoderm in regulation of Tbx5/Tbx4 expression and limb initiation. Saito, D., Yonei-Tamura, S., Takahashi, Y., Tamura, K. Dev. Biol. (2006) [Pubmed]
  10. Virtual cloning and physical mapping of a human T-box gene, TBX4. Yi, C.H., Russ, A., Brook, J.D. Genomics (2000) [Pubmed]
  11. Genitopatellar syndrome: expanding the phenotype and excluding mutations in LMX1B and TBX4. Abdul-Rahman, O.A., La, T.H., Kwan, A., Schlaubitz, S., Barsh, G.S., Enns, G.M., Hudgins, L. Am. J. Med. Genet. A (2006) [Pubmed]
 
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