title: Mesenchymal TGF-β signaling orchestrates dental epithelial stem cell homeostasis through Wnt signaling.
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.
authors: 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; State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, People's Republic of China.
authors: Guan
authors: G
authors: Yang
authors: Jian
authors: J
authors: Zhou
authors: Yan
authors: Y
authors: Teng
authors: Jing
authors: J
authors: Xie
authors: Jingting
authors: J
authors: Lin
authors: Xizhi
authors: X
authors: Guo
authors: Yuanrong
authors: Y
authors: Gao
authors: Miao
authors: M
authors: He
authors: Xiao
authors: X
authors: Yang
authors: Songlin
authors: S
authors: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors
keywords: Dental epithelial stem cell; Dental papilla mesenchymal cell; FGF signaling; Mouse incisor; TGF-β signaling; Wnt signaling