Excess NF-κB Induces Ectopic Odontogenesis in Embryonic Incisor Epithelium

Nuclear factor kappa B (NF-kappa B) signaling plays critical roles in many physiological and pathological processes, including regulating organogenesis. Down-regulation of NF-kappa B signaling during development results in hypohidrotic ectodermal dysplasia. The roles of NF-kappa B signaling in tooth development, however, are not fully understood. We examined mice overexpressing IKK beta, an essential component of the NF-kappa B pathway, under keratin 5 promoter (K5-Ikk beta). K5-Ikk beta mice showed supernumerary incisors whose formation was accompanied by up-regulation of canonical Wnt signaling. Apoptosis that is normally observed in wild-type incisor epithelium was reduced in K5-Ikk beta mice. The supernumerary incisors in K5-Ikk beta mice were found to phenocopy extra incisors in mice with mutations of Wnt inhibitor, Wise. Excess NF-kappa B activity thus induces an ectopic odontogenesis program that is usually suppressed under physiological conditions.