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

Much progress has been made in understanding limb development(1-3). Most ge nes are expressed equally and in the same pattern in the fore- and hindlimb s, which nevertheless develop into distinct structures(3-8). The T-box gene s 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 r evealed that this gene is involved in the transdetermination of Drosophila wing and leg imaginal discs(14). In addition, expression of Tbx5 and Tbx4 c orrelates 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 expre ssed in leg buds(20,21). Here we determine the importance of these factors in establishing limb identity.