p38α MAPK is required for tooth morphogenesis and enamel secretion. Academic Article uri icon

Overview

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 (p38α(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 β4-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.

authors

  • Greenblatt, Matthew Blake
  • Kim, Jung-Min
  • Oh, Hwanhee
  • Park, Kwang Hwan
  • Choo, Min-Kyung
  • Sano, Yasuyo
  • Tye, Coralee E
  • Skobe, Ziedonis
  • Davis, Roger J
  • Park, Jin Mo
  • Bei, Marianna
  • Glimcher, Laurie H
  • Shim, Jae-Hyuck

publication date

  • November 18, 2014

Research

keywords

  • Ameloblasts
  • Dental Enamel
  • Gene Expression Regulation, Developmental
  • Incisor
  • Mitogen-Activated Protein Kinase 14
  • Odontogenesis

Identity

PubMed Central ID

  • PMC4281732

Scopus Document Identifier

  • 84920545982

Digital Object Identifier (DOI)

  • 10.1074/jbc.M114.599274

PubMed ID

  • 25406311

Additional Document Info

volume

  • 290

issue

  • 1