Work

p38α MAPK Is Required for Tooth Morphogenesis and Enamel Secretion

Year: 2014

Type: article

Abstract: An improved understanding of the molecular pathways that drive tooth morphogenesis and enamel secretion is needed to generate teeth from organ cultures for therapeutic implantation or to determine the pathogenesis of primary disorders of dentition (Abdollah, S., Macias-Silva, M., Tsukazaki, T., Hayashi, H., Attisano, L., and Wrana, J. L. (1997) J. Biol. Chem. 272, 27678–27685). Here we present a novel ectodermal dysplasia phenotype associated with conditional deletion of p38α MAPK in ectodermal appendages using K14-cre mice ( p38 α K14 mice). These mice display impaired patterning of dental cusps and a profound defect in the production and biomechanical strength of dental enamel because of defects in ameloblast differentiation and activity. In the absence of p38α, expression of amelogenin and β 4 -integrin in ameloblasts and p21 in the enamel knot was significantly reduced. Mice lacking the MAP2K MKK6, but not mice lacking MAP2K MKK3, also show the enamel defects, implying that MKK6 functions as an upstream kinase of p38α in ectodermal appendages. Lastly, stimulation with BMP2/7 in both explant culture and an ameloblast cell line confirm that p38α functions downstream of BMPs in this context. Thus, BMP-induced activation of the p38α MAPK pathway is critical for the morphogenesis of tooth cusps and the secretion of dental enamel.Little is known regarding the contribution of MAPKs to the development of ectodermal appendages. Results Mice with a deletion of p38α in ectoderm display defective secretion of dental enamel and the absence of dental cusps. Conclusion p38α mediates critical steps in tooth morphogenesis and enamel secretion. Significance This is the first in vivo study demonstrating that the p38 MAPK pathway is critical for tooth morphogenesis and enamel secretion.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m114.599274