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doi: 10.1242/10.1242/dev.00474

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Development 130, 2729-2739 (2003)
Copyright © 2003 The Company of Biologists Limited

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 and Toshihiko Ogura{dagger}

Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0101, Japan
* Present address: Cardiovascular Research, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada

{dagger} Author for correspondence (e-mail: ogura{at}bs.aist-nara.ac.jp).

Accepted 24 February 2003

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.

Key words: Tbx5, Tbx4, Limb initiation, Wnt, Fgf, Chick


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