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

Autor: Jingting Lin, Jian Zhou, Jing Xie, Songlin Wang, Miao He, Yuanrong Gao, Xizhi Guo, Yan Teng, Xiao Yang, Guan Yang
Rok vydání: 2014
Předmět:
Zdroj: Stem Cells. 32:2939-2948
ISSN: 1549-4918
1066-5099
DOI: 10.1002/stem.1772
Popis: 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
Databáze: OpenAIRE
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