Genetic Basis of Supernumerary Tooth
Keywords:
Genetics, odontogenesis, signalling molecules, supernumerary toothAbstract
Odontogenesis is a complex process regulated by both genetic and molecular controls. The development of a tooth in the embryo stage is controlled by a series of signals which occur between tooth-forming epithelium and neural crest-derived ectomesenchyme. Though many genes are involved in tooth formation involving major signalling molecules, the bone morphogenetic protein and fibroblast growth factor are the most important ones involved in odontogenesis. Supernumerary tooth occurs because of imbalance in the expression of the signalling pathways and their inhibitors. This review highlights the various signalling molecules that play a role in odontogenesis in order to provide a better understanding on of the molecular mechanisms involved in the formation of supernumerary tooth in humans.
References
Koussoulakou DS, Margaritis LH, Koussoulakos SL. A curriculum vitae of teeth: evolution, generation, regeneration. International Journal of Biological Sciences. 2009;5(3):226-243.
Huysseune A, Sire JY, Witten PE. Evolutionary and developmental origins of the vertebrate dentition. Journal of Anatomy. 2009;214(4):465-476.
Chinsembu KC. Teeth are bones: signature genes and molecules that underwrite odontogenesis. JMGG. 2012;4(2):13-24.
Schulze C. Developmental abnormalities of the teeth and jaws. 1970. in: Gorlin, R.J., Goldman, H.M. (Eds.), Thomas’s Oral Pathology. Mosby Company, St Louis, pp. 96-183.
Scheiner MA, Sampson WJ. Supernumerary teeth: a review of the literature and four case reports. Australian Dental Journal. 1997;42(3):160-165.
Rajab LD, Hamdan MA. Supernumerary teeth: review of the literature and a survey of 152 cases. International Journal of Paediatric Dentistry. 2002;12(4):244-254.
Pani SC. The genetic basis of tooth agenesis: basic concepts and genes involved. Journal of the Indian Society of Pedodontics and Preventive Dentistry. 2011;29(2):84-89.
Subasioglu A, Savas S, Kucukyilmaz E, Kesim S, Yagci A, Dundar M. Genetic background of supernumerary teeth. European Journal of Dentistry. 2015;9(1):153-158.
Cammarata-Scalisi F, Avendaño A, Callea M. Main genetic entities associated with supernumerary teeth. Archivos Argentinos de PediatriÌa. 2018;116(6):437-444.
Mallineni SK. Supernumerary Teeth: Review of the Literature with Recent Updates. Conference Papers in Science. 2014;2014: Article ID 764050, 6 pages.
Gupta S, Praveen Kumar PS. A study on prevalence, complications, and possible etiologic factors of supernumerary teeth in 6–12‑year‑old schoolchildren of Rohtak, India. Indian Journal of Dental Sciences. 2017;9:141-147.
Tucker AS, Sharpe P. The cutting edge of mammalian development; how the embryo makes teeth. Nature Reviews Genetics. 2004;5(7):499-508.
Sartaj R, Sharpe P. Biological tooth replacement. Journal of Anatomy. 2006;209(4): 503-509.
Ferguson CA, Tucker AS, Sharpe PT. Temporospatial cell interactions regulating mandibular and maxillary arch patterning. Development. 2000;127(2):403-412.
Bei M. Molecular genetics of tooth development. Current Opinion in Genetics & Development. 2009;19(5):504-510.
Brook AH. Multilevel complex interactions between genetic, epigenetic and environmental factors in the aetiology of anomalies of dental development. Archives of Oral Biology. 2009;54(Supp 1): S3-S17.
Nakamura T, Fukumoto S. Genetics of supernumerary tooth formation. Journal of Oral Biosciences. 2013;55(4):180-183.
Williams MA, Letra A. The Changing Landscape in the Genetic Etiology of Human Tooth Agenesis. Genes. 2018;May16;9(5):pii: E255.
Cobourne MT, Sharpe PT. Tooth and jaw: molecular mechanisms of patterning in the first branchial arch. Archives of Oral Biology. 2003;48(1):1-14.
Butler PM. Studies of the mammalian dentition. Differentiation of the post-canine dentition. Proceedings of the Zoological Society of London. 1939;109:1-36.
Galluccio G, Castellano M, La Monaca C. Genetic basis of non-syndromic anomalies of human tooth number. Archives of Oral Biology. 2012;57(7):918-930.
Osborn JW. Morphogenetic gradients: fields versus clones. In: Butler PM, Joysey KA. editors. Development, function and evolution of teeth. Academic Press; London: 1978. pp. 171–201.
Townsend G, Harries EF, Lesot H, Clauss F, Brook AH. Morphogenetic fields within the human dentition: a new clinically relevant synthesis of an old concept. Archives of Oral Biology. 2009;54s: S34-S44.
Klein OD, Minowada G, Peterkova R, Kangas A, Yu BD, Lesot H, Peterka M, Jernvall J, Martin GR. Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signalling. Development Cell. 2006;11(2):181-190.
Fleming PS, Xavier GM, DiBiase AT, Cobourne MT. Revisiting the supernumerary: the epidemiological and molecular basis of extra teeth. British Dental Journal. 2010;208(1):25-30.
Murashima-Suginami A, Takahashi K, Sakata T, Tsukamoto H, Sugai M, Yanagita M, Shimizu A, Sakurai T, Slavkin HC, Bessho K. Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse. Biochemical and Biophysical Research Communications. 2008;369:1012-1016.
Thesleff I, Sharpe P. Signalling networks regulating dental development. Mechanisms of Development. 1997;67(2):111-123.
Mason JM, Morrison DJ, Basson MA. Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signalling. Trends in Cell Biology. 2006;16(1):45-54.
Cobourne MT, Miletich I, Sharpe PT. Restriction of sonic hedgehog signalling during early tooth development. Development. 2004;131(12):2875-2885.
Jernvall J, Thesleff I. Reiterative signalling and patterning during mammalian tooth morphogenesis. Mechanisms of Development. 2000;92(1):19-29.
Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JH, Owen MJ, Mertelsmann R, Zabel BU, Olsen BR. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell. 1997;89(5),773-779.
Schwabe GC, Opitz C, Tinschert S, Mundlos S, Sharpe PT. Molecular mechanisms of tooth development and malformations. Oral Biosciences & Medicine. 2004;1(2):77-91.
Seppala M, Fraser GJ, Birjandi AA, Xavier GM, Cobourne MT. Sonic Hedgehog Signaling and Development of the Dentition. Journal of Developmental Biology. 2017;5(2):6.
Logan CY, Nusse R. The Wnt signalling pathway in development and disease. Annual Review of Cell and Developmental Biology. 2004;20:781-810.
Nakamura T, de Vega S, Fukumoto S, Jimenez L, Unda F, Yamada Y. Transcription factor epiprofin is esssential for tooth morphogenesis by regulating epithelial cell fate and tooth number. Journal of Biological Chemistry. 2008;283(8):4825-4833.
Järvinen E, Salazar-Ciudad I, Birchmeier W, Taketo MM, Jernvall J, Thesleff I. Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin singalling. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(49):18627-18632.
Laurikkala J, Mikkola M, Mustonen T, Ã…berg T, Koppinen P, Pispa J, Nieminen P, Galceran J, Grosschedl R, Thesleff I. TNF signalling via the ligand-receptor pair ectodysplasin and edar controls the function of epithelial signalling centers and is regulated by Wnt and activin during tooth organogenesis. Developmental Biology. 2001;229(2):443-455.
Liu F, Chu EY, Watt B, Zhang Y, Gallant NM, Andl T, Yang SH, Lu MM, Piccolo S, Schmidt-Ullrich R, Taketo MM, Morrisey EE, Atit R, Dlugosz AA, Millar SE. Wnt/beta-catenin signalling directs multiple stages of tooth morphogenesis. Developmental Biology. 2008;313(1):210-224.
Yang J, Wang SK, Choi M, Reid BM, Hu Y, Lee YL, Herzog CR, Kim-Berman H, Lee M, Benke PJ, Lloyd KC, Simmer JP, Hu JC. Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds. Molecular Genetics & Genomic Medicine. 2015;3:40-58.
Sedano HO, Gorlin R. Familial occurrence of mesiodens. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 1969;27(3):360-362.
Thesleff I. Developmental biology and building a tooth. Quintessence International. 2003;34(8):613-620.
Ducy P, Zhang R, Geoffroy V, Ridall A, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997;89:747-754.
Camilleri S, McDonald F. RUNX2 and dental development. European Journal of Oral Sciences. 2006;114(5):361-373.
Quack I, Vonderstrass B, Stock M, Aylsworth AS, Becker A, Brueton L, Lee PJ, Majewski F, Mulliken JB, Suri M, Zenker M, Mundlos S, Otto F. Mutation analysis of core binding factor A1 in patients with cleidocranial dysplasia. American Journal of Human Genetics. 1999;65(5):1268–1278.
Otto F, Kanegane H, Mundlos S. Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Human Mutation. 2002;19(3):209-216.
Currall V, Clancy R, Dimond D, Amirfeyz R, Kershaw C, Gargan M. Cleidocranial dysplasia. Current Orthopaedics. 2007;21(2):159–162.
Kolokitha OE, Papadopoulou AK. Impaction and apical root angulation of the maxillary central incisors due to supernumerary teeth: combined surgical and orthodontic treatment. American Journal of Orthodontics and Dentofacial Orthopedics. 2008;134(1):153-60.
Li Y, Pan W, Xu W, He N, Chen X, Liu H, Darryl Quarles L, Zhou H, Xiao Z. RUNX2 mutations in Chinese patients with cleidocranial dysplasia. Mutagenesis. 2009;24(5):425-431.
Ryoo HM, Kang HY, Lee SK, Lee KE, Kim JW. RUNX2 mutations in cleidocranial dysplasia patients. Oral Diseases. 2010;16(1):55-60.
Tang S, Xu Q, Xu X, Du J, Yang X, Jiang Y, Wang X, Speck N, Huang T. A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails. BMC Medical Genetics. 2007;8:82-88.
Jensen BL, Kreiborg S. Development of the dentition in cleidocranial dysplasia. Journal of Oral Pathology & Medicine. 1990;19(2):89-93.
Pratap J, Galindo M, Zaidi SK, Vradii D, Bhat BM, Robinson JA, Choi JY, Komori T, Stein JL, Lian JB, Stein GS, van Wijnen AJ. Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts. Cancer Research. 2003;63(17):5357-5362.
D’Souza RN, Åberg T, Gaikwad J, Cavender A, Owen M, Karsenty G, Thesleff I. Cbfa 1 is required for epithelial-mesenchymal interactions regulating tooth development in mice. Development. 1999;126(13):2911-2920.
Wang XP, Ã…berg T, James MJ, Levanon D, Groner Y, Thesleff I. RUNX2 (CBFA1) inhibits Shh signalling in the lower but not upper molars of mouse embryos and prevents the budding of putative successional teeth. Journal of Dental Research. 2005;84(2):138-143
Wang XP, O’Connell DJ, Lund JJ, Saadi I, Kuraguchi M, Turbe-Doan A, Cavallesco R, Kim H, Park PJ, Harada H, Kucherlapati R, Maas RL. Apc inhibition of Wnt signalling regulates supernumerary tooth formation during embryogenesis and throughout adulthood. Development. 2009;136(11):1939-1949
Wang XP, Fan J. Molecular genetics of supernumerary tooth formation. Genesis. 2011;49(4):261-277.
Jonason JH, Xiao G, Zhang M, Xing L, Chen D. Post-translational regulation of RUNX2 in bone and cartilage. Journal of Dental Research. 2009;88(8):693-703.
Järvinen E, Shimomura-Kuroki J, Balic A, Jussila M, Thesleff I. Mesenchymal wnt/beta-catenin signaling limits tooth number. Development. 2018;145(4):dev158048.
Jussila M, Thesleff I. Signaling networks regulating tooth organogenesis and regeneration, and the specification of dental mesenchymal and epithelial cell lineages. Cold Spring Harbor Perspectives in Biology. 2012;4:a008425.
Jensen BL, Kreiborg S. Development of the dentition in cleidocranial dysplasia. Journal of Oral Pathology & Medicine. 1990;19:89-93.
Nieminen P, Morgan NV, Fenwick AL, Parmanen S, Veistinen V, Mikkola ML, Giraud A, Judd L, Arte S, Brueton LA, Wall SA, Mathijssen IM, Maher ER, Wilkie AO, Kreiborg S, Thesleff I. Inactivation of IL11 signaling causes craniosynostosis, delayed tooth eruption and supernumerary teeth. American Journal of Human Genetics. 2011;89:67-81.
D’Souza RN, Aberg T, Gaikwad J, Cavender A, Owen M, Karsenty G, Thesleff I. Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice. Development. 1999;126:2911-2920.
Takahashi M, Hosomichi K, Yamaguchi T, Yano K, Funatsu T, Adel M, Haga S, Maki K, Tajima A. Whole-exome sequencing analysis of supernumerary teeth occurrence in Japanese individuals. Human Genome Variation. 2017;4:16046.
D'Souza RN, Klein OD. Unraveling the molecular mechanisms that lead to supernumerary teeth in mice and men: current concepts and novel approaches. Cells Tissues Organs. 2007;186(1):60-69.
Lu X, Yu F, Liu J, Cai W, Zhao Y, Zhao S, Liu S. The epidemiology of supernumerary teeth and the associated molecular mechanism. Organogenesis. 2017;13:3,71-82.
Downloads
Additional Files
Published
Issue
Section
License
JBCS Publication Ethics
JBCS is committed to ensure the publication process follows specific academic ethics. Hence, Authors, Reviewers and Editors are required to conform to standards of ethical guidelines.
Authors
Authors should discuss objectively the significance of research work, technical detail and relevant references to enable others to replicate the experiments. JBCS do not accept fraudulent or inaccurate statements that may constitute towards unethical conduct.
Authors should ensure the originality of their works. In cases where the work and/or words of others have been used, appropriate acknowledgements should be made. JBCS do not accept plagiarism in all forms that constitute towards unethical publishing of an article.
This includes simultaneous submission of the same manuscript to more than one journal. Corresponding author is responsible for the full consensus of all co-authors in approving the final version of the paper and its submission for publication.
Reviewers
Reviewers of JBCS treat manuscripts received for review as confidential documents. Therefore, Reviewers must ensure the confidentiality and should not use privileged information and/or ideas obtained through peer review for personal advantage.
Reviews should be conducted based on academic merit and observations should be formulated clearly with supporting arguments. In cases where selected Reviewer feels unqualified to review a manuscript, Reviewer should notify the editor and excuse himself from the review process in TWO (2) weeks time from the review offer is made.
In any reasonable circumstances, Reviewers should not consider to evaluate manuscripts if they have conflicts of interest (i.e: competitive, collaborative and/or other connections with any of the authors, companies, or institutions affiliated to the papers).
Editors
Editors should evaluate manuscripts exclusively based on their academic merit. JBCS strictly do not allow editors to use unpublished information of authors without the written consent of the author. Editors are required to take appropriate responsive actions if ethical complaints have been presented concerning a submitted manuscript or published paper.
CONFLICT OF INTEREST
Journal of Biomedical and Clinical Sciences requires authors to declare all competing interests in relation to their work. All submitted manuscripts must include a ‘competing interests section at the end of the manuscript listing all competing interests (financial and non-financial). Where authors have no competing interests, the statement should read ,The authors have declared that no competing interests exist. Editors may ask for further information relating to competing interests.
Editors and reviewers are also required to declare any competing interests and will be excluded from the peer review process if a competing interest exists. Competing interests may be financial or non-financial. A competing interest exists when the authors interpretation of data or presentation of information may be influenced by their personal or financial relationship with other people or organizations. Authors should disclose any financial competing interests but also any non-financial competing interests that may cause them embarrassment if they were to become public after the publication of the article.
HUMAN AND ANIMAL RIGHTS
All research must have been carried out within an appropriate ethical framework. If there is suspicion that work has not taken place within an appropriate ethical framework, Editors will follow the Misconduct policy and may reject the manuscript, and/or contact the author(s) institution or ethics committee. On rare occasions, if the Editor has serious concerns about the ethics of a study, the manuscript may be rejected on ethical grounds, even if approval from an ethics committee has been obtained.
Research involving human subjects, human material, or human data, must have been performed in accordance with the Declaration of Helsinki and must have been approved by an appropriate ethics committee. A statement detailing this, including the name of the ethics committee and the reference number where appropriate, must appear in all manuscripts reporting such research. Further information and documentation to support this should be made available to Editors on request.
Experimental research on vertebrates or any regulated invertebrates must comply with institutional, national, or international guidelines, and where available should have been approved by an appropriate ethics committee. The Basel Declaration outlines fundamental principles to adhere to when conducting research in animals and the International Council for Laboratory Animal Science (ICLAS) has also published ethical guidelines.
A statement detailing compliance with relevant guidelines (e.g. the revised Animals (Scientific Procedures) Act 1986 in the UK and Directive 2010/63/EU in Europe) and/or ethical approval (including the name of the ethics committee and the reference number where appropriate) must be included in the manuscript. The Editor will take account of animal welfare issues and reserves the right to reject a manuscript, especially if the research involves protocols that are inconsistent with commonly accepted norms of animal research. In rare cases, Editors may contact the ethics committee for further information.
INFORMED CONSENT
For all research involving human subjects, informed consent to participate in the study should be obtained from participants (or their parent or guardian in the case of children under 16) and a statement to this effect should appear in the manuscript, this includes to all manuscripts that include details, images, or videos relating to individual participants.
DATA SHARING POLICY
JBCS strongly encourages that all datasets on which the conclusions of the paper rely should be available to readers. We encourage authors to ensure that their datasets are either deposited in publicly available repositories (where available and appropriate) or presented in the main manuscript or additional supporting files, in machine-readable format (such as spreadsheets rather than PDFs) whenever possible
Authors who do not wish to share their data must state that data will not be shared, and give the reason.
COPYRIGHT NOTICE
The JBCS retains the copyright of published manuscripts under the terms of the Copyright Transfer Agreement. However, the journal permits unrestricted use, distribution, and reproduction in any medium, provided permission to reuse, distribute and reproduce is obtained from the Journal's Editor and the original work is properly cited.
While the advice and information in this journal are believed to be true and accurate on the date of its going to press, neither the authors, the editors, nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.
Copyright (c) 2023 Journal of Biomedical and Clinical Sciences (JBCS)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
