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

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.