Excess NF-κB induces ectopic odontogenesis in embryonic incisor epithelium.
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.
J
J
Blackburn
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.
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K
Kawasaki
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.
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T
Porntaveetus
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.
M
M
Kawasaki
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.
Y
Y
Otsuka-Tanaka
Department of Ultrastructural Science, Tokyo Dental College, Chiyoda-ku, Tokyo, Japan.
Y
Y
Miake
Laboratory of Food Biological Science, Department of Food and Nutrition, Japan Women's University, Bunkyō, Japan.
M S
MS
Ota
Division of Oral Anatomy, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
M
M
Watanabe
Department of Special Needs Dentistry, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
M
M
Hishinuma
Department of Special Needs Dentistry, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
T
T
Nomoto
Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK.
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S
Oommen
Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK.
S
S
Ghafoor
Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK.
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F
Harada
Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK.
K
K
Nozawa-Inoue
Division of Oral Anatomy, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
T
T
Maeda
Department of Teratology, Institute of Experimental Medicine, Academy of Sciences CR, Prague, Czech Republic.
R
R
Peterková
INSERM UMR_S1109, Team "Osteoarticular and Dental Regenerative NanoMedicine," FMTS, Faculté de Médecine, Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
H
H
Lesot
Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
J
J
Inoue
Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
T
T
Akiyama
Department of Signal Transduction in Tumor Cells, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
R
R
Schmidt-Ullrich
Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX, USA.
B
B
Liu
Laboratory of Experimental Immunology, Inflammation and Tumorigenesis Section, National. Cancer Institute-Frederick, Frederick, MD, USA.
Y
Y
Hu
Department of Epithelial Biomedicine, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain.
A
A
Page
Department of Epithelial Biomedicine, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain.
Á
Á
Ramírez
Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK paul.sharpe@kcl.ac.uk atsushiohazama@dent.niigata-u.ac.jp.
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PT
Sharpe
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 paul.sharpe@kcl.ac.uk atsushiohazama@dent.niigata-u.ac.jp.
A
A
Ohazama
D048868:Adaptor Proteins, Signal Transducing; D000565:Ameloblasts / Q000166:cytology; D053523:Amelogenin / Q000032:analysis; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D003743:Dental Enamel / Q000166:cytology; D004848:Epithelium / Q000196:embryology; D053823:Hedgehog Proteins / Q000502:physiology; D051550:I-kappa B Kinase / Q000502:physiology; D021621:Imaging, Three-Dimensional / Q000379:methods; D007180:Incisor / Q000002:abnormalities / Q000196:embryology*; D053569:Keratin-15 / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008852:Microradiography / Q000379:methods; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000502:physiology*; D009805:Odontogenesis / Q000502:physiology*; D000072079:Patched Receptors; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology; D014083:Tooth Germ / Q000002:abnormalities / Q000196:embryology*; D014096:Tooth, Supernumerary / Q000209:etiology / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology; D055114:X-Ray Microtomography / Q000379:methods
D048868:Adaptor Proteins, Signal Transducing; D053523:Amelogenin; D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D053569:Keratin-15; C492053:Krt15 protein, mouse; D016328:NF-kappa B; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; C465570:Shh protein, mouse; C483887:Sostdc1 protein, mouse; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase
Ikkβ; Wnt signaling; cervical loop; enamel; tooth development; wise