Gsk3β Is Required in the Epithelium for Palatal Elevation in Mice

In Wnt/beta-catenin signaling pathway, Gsk3 beta functions to facilitate beta-catenin degradation. Inactivation of Gsk3 beta in mice causes a cleft palate formation, suggesting an involvement of Wnt/beta-catenin signaling during palatogenesis. In this study, we have investigated the expression pattern, tissue-specific requirement and function of Gsk3 beta during mouse palatogenesis. We showed that Gsk3 beta is primarily expressed in the palatal epithelium, particularly in the medial edge epithelium overlapping with b-catenin. Tissue-specific gene inactivation studies demonstrated an essential role for Gsk3 beta in the epithelium for palate elevation, and disruption of which contributes to cleft palate phenotype in Gsk3 beta mutant. We observed that expression of Aixn2, a direct target gene of Wnt/beta-catenin signaling, is ectopically activated in the mutant tongue, but not in the palate. Our results indicate that Gsk3 beta is an intrinsic regulator required in the epithelium for palate elevation, and could act through a pathway independent of Wnt/beta-catenin signaling to regulate palate development. Developmental Dynamics 239:3235-3246, 2010. (C) 2010 Wiley-Liss, Inc.