Asymmetric Requirement of Surface Epithelial β-Catenin During the Upper and Lower Jaw Development

Background: Intercellular communication between epithelial and mesenchymal cells is central to mammalian craniofacial development. β-catenin is the gateway of canonical Wnt signaling, one of the major evolutionarily conserved cell–cell communication pathways in metazoa. In this study, we report an unexpected stage- and tissue-specific function of β-catenin during mammalian jaw development. Results: Using a unique mouse genetic tool, we have discovered that epithelial β-catenin is essential for lower jaw formation, while attenuation of β-catenin is required for proper upper jaw development. Changes in β-catenin in vivo alter major epithelial Fgf8, Bmp4, Shh, and Edn1 signals, resulting in partial transcriptional reprogramming of the neural crest-derived mesenchyme, the primary source of jawbones. Conclusions: The Wnt/β-catenin signal coordinates expression of multiple epithelial signals and has stage-specific asymmetric functions during mammalian upper and lower jaw development. In addition, these findings suggest that evolutionary changes of the canonical Wnt/β-catenin signaling pathway may lead to innovation of jaws. Developmental Dynamics 241:663–674, 2012. © 2012 Wiley Periodicals, Inc. KEY FINDINGS: Mammalian epithelial Wnt/β-catenin signaling has asymetric functions in the upper and lower jaw development. The canonical Wnt/β-catenin pathway coordinates expression of multiple epithelial signals including Fgf8, Bmp4, Shh, and Edn1. Activation of epithelial Wnt/β-catenin signaling induces molecular transformation of the upper jaw to the lower jaw mesenchymal phenotype. Evolutionary changes of the canonical Wnt/β-catenin signaling pathway may lead to innovation of jaws.