T-box genes and the evolution of paired vertebrate appendages.

Modern jawed vertebrates possess two sets of paired appendages. The specific molecular genetic events associated with their origin remain enigmatic. Recently we suggested that certain T-box genes, transcription factors playing essential roles in vertebrate embryogenesis, were involved in the transition from a limbless ancestral chordate into a modern vertebrate with two sets of paired appendages. In tetrapods, Tbx5 and Tbx4 are expressed in the fore- and hindlimb fields, respectively, prior to the initiation of limb bud formation, and are likely to be responsible for determining limb identity. We will demonstrate that, prior to the advent of jawed vertebrates, these two genes diverged from a common ancestral locus within the vertebrate lineage. Comparative developmental data indicate that limb- related gene functions were first established, and subsequently maintained, shortly following gene divergence. We will propose a model, which incorporates palaeontological, developmental, and genetic data, to argue that gene duplication followed by differential regulation of these genes was a major driving force in the evolution of paired vertebrate appendage.