Mesenchymal TGF-β Signaling Orchestrates Dental Epithelial Stem Cell Homeostasis Through Wnt Signaling

Authors

  • Guan Yang,

    1. Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People's Republic of China
    2. State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, People's Republic of China
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  • Jian Zhou,

    1. Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People's Republic of China
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  • Yan Teng,

    1. State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, People's Republic of China
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  • Jing Xie,

    1. State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, People's Republic of China
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  • Jingting Lin,

    1. State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, People's Republic of China
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  • Xizhi Guo,

    1. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, People's Republic of China
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  • Yuanrong Gao,

    1. Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People's Republic of China
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  • Miao He,

    1. Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People's Republic of China
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  • Xiao Yang,

    Corresponding author
    1. State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, People's Republic of China
    • Correspondence: Songlin Wang, D.D.S., Ph.D., Capital Medical University School of Stomatology, Tian Tan Xi Li No.4, Beijing 100050, People's Republic of China. Telephone: 86-10-83911708; Fax: 86-10-83911708; e-mail: slwang@ccmu.edu.cn; or Xiao Yang, Ph.D., Institute of Biotechnology, 20 Dongdajie, Beijing 100071, People's Republic of China. Telephone: 86-10-63895937; Fax: 86-10-63895937; e-mail: yangx@bmi.ac.cn

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  • Songlin Wang

    Corresponding author
    1. Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People's Republic of China
    • Correspondence: Songlin Wang, D.D.S., Ph.D., Capital Medical University School of Stomatology, Tian Tan Xi Li No.4, Beijing 100050, People's Republic of China. Telephone: 86-10-83911708; Fax: 86-10-83911708; e-mail: slwang@ccmu.edu.cn; or Xiao Yang, Ph.D., Institute of Biotechnology, 20 Dongdajie, Beijing 100071, People's Republic of China. Telephone: 86-10-63895937; Fax: 86-10-63895937; e-mail: yangx@bmi.ac.cn

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Abstract

In mouse, continuous growth of the postnatal incisor is coordinated by two populations of multipotent progenitor cells, the dental papilla mesenchymal cells and dental epithelial stem cells, residing at the proximal end of the incisor, yet the molecular mechanism underlying the cooperation between mesenchymal and epithelial cells is largely unknown. Here, transforming growth factor-β (TGF-β) type II receptor (Tgfbr2) was specifically deleted within the postnatal dental papilla mesenchyme. The Tgfbr2-deficient mice displayed malformed incisors with wavy mineralized structures at the labial side as a result of increased differentiation of dental epithelial stem cells. We found that mesenchymal Tgfbr2 disruption led to upregulated expression of Wnt5a and downregulated expression of Fgf3/10 in the mesenchyme, both of which synergistically enhanced Lrp5/6-β-catenin signaling in the cervical loop epithelium. In accord with these findings, mesenchyme-specific depletion of the Wnt transporter gene Wls abolished the aberrant mineralized structures caused by Tgfbr2 deletion. Thus, mesenchymal TGF-β signaling provides a unifying mechanism for the homeostasis of dental epithelial stem cells via a Wnt signaling-mediated mesenchymal-epithelial cell interaction. Stem Cells 2014;32:2939–2948

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