Wnt signaling in lip and palate development.

Wnt signaling regulates a variety of cell behaviors and represents a major pathway in development and disease. Mutations in Wnt genes and their downstream targets have been implicated in human craniofacial abnormalities, including the most prevalent birth defect, cleft lip with or without palate. Formation of the upper lip and palate is a complicated process and is composed of a series of highly coordinated steps during tissue morphogenesis, which are rigorously controlled by genetic networks. While genetic controls of lip/palate development have been extensively studied, the roles of Wnt signaling in these processes remained poorly understood. Within the cell, Wnt signaling is transduced in a β-catenin-dependent (canonical) or -independent (non-canonical) fashion. Recent studies have demonstrated that the canonical and non-canonical pathways play differential roles but both are essential in lip/palate development. Here we review these studies that have substantially advanced our knowledge by elucidating the function of Wnt signaling in upper lip formation, secondary palate development and their disease settings. These advances are important to delineate the genetic networks controlling craniofacial development and to develop personalized therapeutic strategies in related human birth defects in the future.