As previously stated, limb development is essentially autonomous after the signaling centers (AER) and ZPA) have been established. However, it is important to know that Hox genes continue to participate in the dynamic regulation of limb development even after the AER and ZPA have been established in the limb bud. Complex communication ensues as AER-secreted FGF signals and ZPA-secreted Shh signals initiate and regulate Hox gene expression in the developing limb bud. Though many of the finer details remain to be resolved, a number of significant connections between Hox gene expression and the impact on limb development have been discovered.