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Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds

Abstract

Much progress has been made in understanding limb development1,2,3. Most genes are expressed equally and in the same pattern in the fore- and hindlimbs, which nevertheless develop into distinct structures3,4,5,6,7,8. The T-box genes Tbx5 and Tbx4, on the other hand, are expressed differently in chick wing (Tbx5) and leg (Tbx4) buds9,10,11,12. Molecular analysis of the optomotor blind gene13, which belongs to the same family of transcription factors, has revealed that this gene is involved in the transdetermination of Drosophila wing and leg imaginal discs14. In addition, expression of Tbx5 and Tbx4 correlates well with the identity of ectopic limb buds induced by fibroblast growth factor4,5,15,16,17,18,19. Thus, it is thought that Tbx5 and Tbx4 might be involved in determining limb identity. Another candidate is the Pitx1 gene, which encodes a bicoid-type homeodomain transcription factor that is expressed in leg buds20,21. Here we determine the importance of these factors in establishing limb identity.

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Figure 1: Misexpression of Tbx5 and Tbx4 converts the wing/leg identity of limb buds.
Figure 2: Tbx5 and Tbx4 regulate Hoxc9/d9 expression in the developing limb buds.
Figure 3: Limb identities of the extra limbs induced in the flank by the mixed-cell aggregates of Tbx4/FGF8.
Figure 4: The regulatory network of the Tbx5, Tbx4 and Pitx1 genes.
Figure 5: Interactions regulating the wing/leg identity of limb buds.

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Acknowledgements

We thank C. Campbell for human TBX2 cDNA plasmid pQE9Eag; J. C. Izpisua-Belmonte for chicken Hoxd9; A. Kuroiwa for chicken Hoxb9 and c9 probes; K. Umesono and R. Yu for critically reading the manuscript and for helpful comments; and T. Momose for technical assistance in the electroporation system. This study was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan, and by special coordination funds for promoting science and technology from the Science and Technology Agency. A.V.-H. was supported by a grant from the Deutsche Forschungsgemeinschaft and a foreign fellowship from the Japan Society for the Promotion of Sciences. This paper is dedicated to K. Umesono.

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Correspondence to Toshihiko Ogura.

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Takeuchi, J., Koshiba-Takeuchi, K., Matsumoto, K. et al. Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds. Nature 398, 810–814 (1999). https://doi.org/10.1038/19762

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