A dual role for lkkalpha in tooth development


  • A. Ohazama
  • Y.L. Hu
  • R. Schmidt-Ullrich
  • Y.X. Cao
  • C. Scheidereit
  • M. Karin
  • P.T. Sharpe


  • Developmental Cell


  • Dev Cell 6 (2): 219-227


  • IKK{alpha} is a component of the I{kappa}B kinase (IKK) complex that plays a key role in the activation of NF-{kappa}B. In Ikk{alpha} mutant mice and mice expressing a transdominant negative mutant of I{kappa}B{alpha} (cI{kappa}B{alpha}ΔN), molars have abnormal cusps, indicating that Ikk{alpha} is involved in cusp formation through the NF-{kappy}B pathway. However, Ikk{alpha} mutant incisors also have an earlier phenotype where epithelium evaginates outward into the developing oral cavity rather than invaginating into the underlying mesenchyme. A similar evagination of epithelium was also observed in whisker development, suggesting that Ikk{alpha} contributes to the direction of epithelial growth during the early stages of development in many ectodermal appendages. Since cI{kappa}B{alpha}ΔN mice have normal incisor epithelial invagination, Ikk{alpha}'s role appears to be NF-{kappa}B independent. Changes in Notch1, Notch2, Wnt7b, and Shh expression found in incisor epithelium of Ikk{alpha} mutants suggest that this NF-{kappa}B-independent function is mediated by Notch/Wnt/Shh signaling pathways.