Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation

Guilherme Xavier; Amanda Louise Patist; Christopher Paul Healy; Ankita Pagrut; G Carreno; Paul Thomas Sharpe; J P Martinez-Barbera; Selvam James Thavaraj; Martyn Timothy Cobourne; Cynthia Andoniadou

doi:10.1038/srep14479

Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation

Guilherme Xavier, Amanda Louise Patist, Christopher Paul Healy, Ankita Pagrut, G Carreno, Paul Thomas Sharpe, J P Martinez-Barbera, Selvam James Thavaraj, Martyn Timothy Cobourne, Cynthia Andoniadou^*

^*Corresponding author for this work

King's College London

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

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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.

Original language	English
Article number	14479
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep14479
Publication status	Published - 28 Sept 2015

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Activated WNT signaling_XAVIER_Published 2014_GOLD VoRFinal published version, 1.83 MBLicence: CC BY

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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.",

author = "Guilherme Xavier and Patist, {Amanda Louise} and Healy, {Christopher Paul} and Ankita Pagrut and G Carreno and Sharpe, {Paul Thomas} and Martinez-Barbera, {J P} and Thavaraj, {Selvam James} and Cobourne, {Martyn Timothy} and Cynthia Andoniadou",

year = "2015",

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doi = "10.1038/srep14479",

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T1 - Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation

AU - Xavier, Guilherme

AU - Patist, Amanda Louise

AU - Healy, Christopher Paul

AU - Pagrut, Ankita

AU - Carreno, G

AU - Sharpe, Paul Thomas

AU - Martinez-Barbera, J P

AU - Thavaraj, Selvam James

AU - Cobourne, Martyn Timothy

AU - Andoniadou, Cynthia

PY - 2015/9/28

Y1 - 2015/9/28

N2 - 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.

AB - 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.

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Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation

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