Fig. 7. Models for the interactions between dHand, Gli3 and Tbx3, in the limb-forming region at stages prior to Shh expression, that refine limb position along the rostrocaudal axis of the embryo. (A) At stage 16, Tbx3 is expressed throughout the limb-forming region but expression is more robust in the future posterior limb mesenchyme. dHand is expressed throughout the limb-forming region. (B) At stage 17, Gli3 is expressed throughout the limb mesenchyme with higher levels in the anterior. dHand expression is restricted to the posterior. (C) Ectopic expression of Tbx3 in more anterior regions leads to a repression of Gli3, resulting in a de-repression of dHand and expansion of its expression domain. (D) A model illustrating how the genetic antagonism between dHand and Gli3 that positions the future ZPA may be mediated through Tbx3. – and + symbols indicate, respectively, the transcriptional repressor and activator function of each protein. In addition, in the posterior limb, Tbx3 and dHand cooperate to induce Shh expression and thereby specify the position of the ZPA in the posterior limb mesenchyme. A, anterior; P, posterior.