Abstract
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 FindingsMammalian 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.
Highlights
Exquisite vertebrate facial structures are results of gradual transformations of relatively simple embryonic mesenchymal swellings or prominences, including bthe first pharyngeal arch (PA1; Helms and Schneider, 2003; Santagati and Rijli, 2003; Kuratani, 2005; Depew and Simpson, 2006)
We demonstrated that epithelial b-catenin coordinates expression of several critical signaling molecules required for vertebrate jaw development
We found that high levels of epithelial b-catenin support lower jaw development while inducing molecular reprogramming of mesenchymal cells from a maxillary to mandibular-like fate
Summary
Intercellular communication between epithelial and mesenchymal cells is central to mammalian craniofacial development. b-catenin is the gateway of canonical Wnt signaling, one of the major evolutionarily conserved cell–cell communication pathways in metazoa. Changes in b-catenin in vivo alter major epithelial Fgf, Bmp, Shh, and Edn signals, resulting in partial transcriptional reprogramming of the neural crest-derived mesenchyme, the primary source of jawbones. Conclusions: The Wnt/b-catenin signal coordinates expression of multiple epithelial signals and has stage-specific asymmetric functions during mammalian upper and lower jaw development. These findings suggest that evolutionary changes of the canonical Wnt/b-catenin signaling pathway may lead to innovation of jaws. VC 2012 Wiley Periodicals, Inc. Key Findings: Mammalian epithelial Wnt/b-catenin signaling has asymetric functions in the upper and lower jaw development. The canonical Wnt/b-catenin pathway coordinates expression of multiple epithelial signals including Fgf, Bmp, Shh, and Edn. Evolutionary changes of the canonical Wnt/b-catenin signaling pathway may lead to innovation of jaws
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