Nuclear factor kappa B (NF-κB) signaling plays critical roles in many physiological and pathological processes, including regulating organogenesis. Down-regulation of NF-κB signaling during development results in hypohidrotic ectodermal dysplasia. The roles of NF-κB signaling in tooth development, however, are not fully understood. We examined mice overexpressing IKKβ, an essential component of the NF-κB pathway, under keratin 5 promoter (K5-Ikkβ). K5-Ikkβ 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-Ikkβ mice. The supernumerary incisors in K5-Ikkβ mice were found to phenocopy extra incisors in mice with mutations of Wnt inhibitor, Wise. Excess NF-κB activity thus induces an ectopic odontogenesis program that is usually suppressed under physiological conditions.

Craniofacial Development and Stem Cell Biology and Biomedical Research Centre Kings College London London UK

Craniofacial Development and Stem Cell Biology and Biomedical Research Centre Kings College London London UK Department of Pediatric Dentistry Niigata University Graduate School of Medical and Dental Sciences Niigata Japan

Craniofacial Development and Stem Cell Biology and Biomedical Research Centre Kings College London London UK Department of Physiology Faculty of Dentistry Chulalongkorn University Bangkok Thailand

Craniofacial Development and Stem Cell Biology and Biomedical Research Centre Kings College London London UK Department of Special Needs Dentistry Nihon University School of Dentistry at Matsudo Matsudo Japan

Craniofacial Development and Stem Cell Biology and Biomedical Research Centre Kings College London London UK Division of Bio Prosthodontics Department of Oral Health Science Course for Oral Life Science Niigata University Graduate School of Medical and Dental Sciences Niigata Japan

Craniofacial Development and Stem Cell Biology and Biomedical Research Centre Kings College London London UK Division of Oral Anatomy Department of Oral Biological Science Niigata University Graduate School of Medical and Dental Sciences Niigata Japan

Department of Epithelial Biomedicine Centro de Investigaciones Energéticas Medioambientales y Tecnológicas Madrid Spain

Department of Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville TX USA

Department of Signal Transduction in Tumor Cells Max Delbrück Center for Molecular Medicine Berlin Germany

Department of Special Needs Dentistry Nihon University School of Dentistry at Matsudo Matsudo Japan

Department of Teratology Institute of Experimental Medicine Academy of Sciences CR Prague Czech Republic

Department of Ultrastructural Science Tokyo Dental College Chiyoda ku Tokyo Japan

Division of Cellular and Molecular Biology Institute of Medical Science University of Tokyo Minato ku Tokyo Japan

Division of Oral Anatomy Department of Oral Biological Science Niigata University Graduate School of Medical and Dental Sciences Niigata Japan

INSERM UMR_S1109 Team Osteoarticular and Dental Regenerative NanoMedicine FMTS Faculté de Médecine Faculté de Chirurgie Dentaire Université de Strasbourg Strasbourg France

Laboratory of Experimental Immunology Inflammation and Tumorigenesis Section National Cancer Institute Frederick Frederick MD USA

Laboratory of Food Biological Science Department of Food and Nutrition Japan Women's University Bunkyō Japan

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Role of Cell Death in Cellular Processes During Odontogenesis