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

Abstract

Eyelid closure is required for the development of multiple ocular tissues. Interactions between the epithelium and underlying mesenchyme play a pivotal role in regulating eyelid development. However, the molecular mechanisms underlying these interactions remain unclear. Wnt signaling pathways regulate the development of ocular tissues, but their functions in eyelid development are not fully defined. In this study, we find that 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 developing, similar to the effects of deleting mesenchymal {beta}-catenin, suggesting that mesenchymal Wnt/{beta}- catenin signaling is controlled by epithelial Wnt ligands during eyelid development. We also found that deletion of p63 results in formation of hypoplastic eyelids and reduced expression of several Wnt ligands in eyelid epithelium, indicating that expression of Wnt ligands in eyelid development is at least partially regulated by p63. Taken together, our data indicate that Wnt/{beta}-catenin signaling controls eyelid growth by orchestrating epithelial- mesenchymal interactions.