β‐Catenin‐dependent Wnt signaling in apical ectodermal ridge induction and FGF8 expression in normal and limbless mutant chick limbs

The fibroblast growth factor (FGF) and β‐catenin‐dependent Wnt signaling pathways are key regulators of vertebrate limb development. FGF10 induces expression of Wnt3a, which regulates the formation and FGF8 expression of the apical ectodermal ridge (AER). In amelic limbless limbs, an AER fails to form and FGF8 is not expressed, despite expression of FGF10. It has been found that Wnt3a is initially expressed in limbless ectoderm, although subsequently is drastically reduced. In addition, changes in the expression pattern or level of several Frizzled receptors, Axin, Lef1/Tcf1 and β‐catenin have been found in limbless limbs. Notably, while normal wing buds respond to LiCl‐stimulated activation of β‐catenin‐dependent signaling by forming ectopic, FGF8‐expressing AER, LiCl was unable to induce an AER in limbless wing buds. The results of this study suggest that the limbless gene is required for β‐catenin‐dependent Wnt signaling in limb ectoderm leading to FGF8 expression and AER formation.