Tbx5 and Tbx4 trigger limb initiation through activation of the Wnt/Fgf signaling cascade

Jun K. Takeuchi, Kazuko Koshiba-Takeuchi, Takayuki Suzuki, Mika Kamimura, Keiko Ogura, Toshihiko Ogura

Research output: Contribution to journalReview articlepeer-review

131 Citations (Scopus)


A tight loop between members of the fibroblast growth factor and the Wnt families plays a key role in the initiation of vertebrate limb development. We show for the first time that Tbx5 and Tbx4 are directly involved in this process. When dominant-negative forms of these Tbx genes were misexpressed in the chick prospective limb fields, a limbless phenotype arose with repression of both Wnt and Fgf genes By contrast, when Tbx5 and Tbx4 were misexpressed in the flank, an additional wing-like and an additional leg-like limbs were induced, respectively. 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.

Original languageEnglish
Pages (from-to)2729-2739
Number of pages11
Issue number12
Publication statusPublished - 2003 Jun
Externally publishedYes


  • Chick
  • Fgf
  • Limb initiation
  • Tbx4
  • Tbx5
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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