Fig. 7. A proposed model for Tbx4 function in the hindlimb. During hindlimb initiation in normal embryos, dHand is repressed in the anterior but not the posterior limb bud by the FGF-dependent action of Gli3. Simultaneously, Fgf10 signals to the overlying ectoderm to upregulate Fgf8. As the limb bud progresses, dHand repression in the anterior limb bud is maintained, while Fgf8 reciprocal signaling maintains Fgf10 in the limb mesenchyme. In the mutant hindlimb bud, failure of Tbx4-mediated FGF signaling leads to derepression of dHand in the anterior limb bud. Mesenchymal FGF signaling to the ectoderm is normal and Fgf8 is properly upregulated, but reciprocal signaling fails and Fgf10 is not maintained.