title: Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation.
abstract: In common with most mammals, humans form only two dentitions during their lifetime. Occasionally, supernumerary teeth develop in addition to the normal complement. Odontoma represent a small group of malformations containing calcified dental tissues of both epithelial and mesenchymal origin, with varying levels of organization, including tooth-like structures. The specific cell type responsible for the induction of odontoma, which retains the capacity to re-initiate de novo tooth development in postnatal tissues, is not known. Here we demonstrate that aberrant activation of WNT signaling by expression of a non-degradable form of β-catenin specifically in SOX2-positive postnatal dental epithelial stem cells is sufficient to generate odontoma containing multiple tooth-like structures complete with all dental tissue layers. Genetic lineage-tracing confirms that odontoma form in a similar manner to normal teeth, derived from both the mutation-sustaining epithelial stem cells and adjacent mesenchymal tissues. Activation of the WNT pathway in embryonic SOX2-positive progenitors results in ectopic expression of secreted signals that promote odontogenesis throughout the oral cavity. Significantly, the inductive potential of epithelial dental stem cells is retained in postnatal tissues, and up-regulation of WNT signaling specifically in these cells is sufficient to promote generation and growth of ectopic malformations faithfully resembling human odontoma.
authors.affiliation: Department of Orthodontics, King's College London, UK.|Department of Craniofacial Development and Stem Cell Biology, King's College London, UK.
authors.forename: Guilherme M
authors.initials: GM
authors.lastname: Xavier
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, UK.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Patist
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Healy
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, UK.
authors.forename: Ankita
authors.initials: A
authors.lastname: Pagrut
authors.affiliation: Developmental Biology and Cancer Programme, Birth Defects Research Centre, Institute of Child Health, University College London, UK.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Carreno
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
authors.affiliation: Developmental Biology and Cancer Programme, Birth Defects Research Centre, Institute of Child Health, University College London, UK.
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Martinez-Barbera
authors.affiliation: Department of Mucosal and Salivary Biology, King's College London, UK.
authors.forename: Selvam
authors.initials: S
authors.lastname: Thavaraj
authors.affiliation: Department of Orthodontics, King's College London, UK.|Department of Craniofacial Development and Stem Cell Biology, King's College London, UK.
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Cobourne
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, UK.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Andoniadou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D009805:Odontogenesis / Q000235:genetics; D009810:Odontoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D055748:SOXB1 Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin