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

Much progress has been made in understanding limb development(1-3). Most genes are expressed equally and in the same pattern in the fore- and hindlimbs, which nevertheless develop into distinct structures(3-8). The T-box genes Tbx5 and Tbx4 on the other hand, are expressed differently in chick wing (Tbx5) and leg (Tbx4) buds(9-12). Molecular analysis of the optomotor blind gene(13), 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 discs(14). In addition, expression of Tbx5 and Tbx4 correlates well with the identity of ectopic limb buds induced by fibroblast growth factor(4,5,15-19). 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 buds(20,21). Here we determine the importance of these factors in establishing limb identity.