Tbx3 can alter limb position along the rostrocaudal axis of the developing embryo

The limbs of the vertebrate embryo form at precise locations along the body and these positions are fixed across different species. The mechanisms that control this process are not understood. Ectopic expression of Tbx3, a transcriptional repressor that belongs to the Tbx2/3/4/5 subfamily of T-box transcriptional regulators, in the forelimb results in a rostral shift in the position of the limb along the main body axis. By contrast, a transcriptional activator form of Tbx3 shifts the limb to more caudal locations. We also show that dHand and Gli3, genes previously implicated in anteroposterior pre-patterning of the limb-forming region, are also involved in refining the position of the limbs. Our data suggest a new role for Tbx3 in positioning the limb along the main body axis through a genetic interplay between dHand and Gli3.