The T-box genes Tbx4 and Tbx5 regulate limb outgrowth and identity

During embryonic development, initially similar fields can develop into dis tinct structures, such as the vertebrate fore- and hindlimbs, Although cons iderable progress has been made in our understanding of the genetic control underlying the establishment of the different Limb axes(1-3), the molecula r cues that specify the differential development of the fore- and hindlimbs are unknown. Possible candidates for genes determining limb identity are P itxI, a gene whose transcripts are detected in the early hind- but not fore limb bud, and two members of the T-box (Tbx) gene family, Tbx4 and Tbx5, wh ich are specifically expressed in the hindlimb and forelimb buds, respectiv ely(4-6). Here we show that Tbx4 and Tbx5 are essential regulators of limb outgrowth whose roles seem to be tightly linked to the activity of three si gnalling proteins that are required for limb outgrowth and patterning: fibr oblast growth factor (FGF), bone morphogenetic protein (BMP) and Wnt. In ad dition, we provide evidence that Tbx4 and Tbx5 are involved in controlling limb identity. Our findings provide insight into how similar developmental fields can evolve into homologous but distinct structures.