A dual role for lkkα in tooth development

IKKalpha is a component of the IkappaB kinase (IKK) complex that plays a key role in the activation of NF-kappaB. In Ikkalpha mutant mice and mice expressing a transdominant negative mutant Of IkappaBalpha (C-IkappaBalphaDeltaN), molars have abnormal cusps, indicating that Ikka is involved in cusp formation through the NF-kappaB pathway. However, Ikka 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 Ikkalpha contributes to the direction of epithelial growth during the early stages of development in many ectodermal appendages. Since C-IkappaBalphaDeltaN mice have normal incisor epithelial invagination, Ikkalpha's role appears to be NF-kappaB independent. Changes in Notch1, Notch2, Wnt7b, and Shh expression found in incisor epithelium of Ikkalpha mutants suggest that this NF-kappaB-independent function is mediated by Notch/Wnt/Shh signaling pathways.