Wnt/β-catenin signaling controls mouse eyelid growth by mediating epithelial-mesenchymal interactions

Purpose: To investigate the role of Wnt/beta-catenin signaling in mouse eyelid development. Methods: Wnt/beta-catenin signaling was disrupted by deleting supraorbital mesenchymal beta-catenin or epithelial Wls. p63 was removed to determine whether the expression of Wnts is affected. The eyelid morphology was examined at different stages. Proliferation, apoptosis, and expression of Wnt ligands and their target genes were analyzed via immunofluorescence staining, TUNEL assay, and in situ hybridization. Results: Deletion of beta-catenin in supraorbital mesenchyme abolishes eyelid growth by causing decreased proliferation in supraorbital epithelium and underlying mesenchyme. Inhibition of Wnt secretion by deleting Wls in supraorbital epithelium results in failure of eyelid development, similar to the effects of deleting mesenchymal beta-catenin. Knockout of p63 results in formation of hypoplastic eyelids and reduced expression of several Wnt ligands in eyelid epithelium. Conclusions: Epithelial Wnt ligands activate mesenchymal Wnt/beta-catenin signaling to control eyelid growth and their expression is partially regulated by p63.