期刊
DEVELOPMENT
卷 140, 期 21, 页码 4375-4385出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.097733
关键词
beta-catenin signaling; FGF; Tooth development
资金
- National Institutes of Health/National Institute of Dental and Craniofacial Research grants [R01 DE17792, DE14044]
- '973' Project from the Ministry of Science and Technology of China [2010CB944800]
- National Natural Science Foundation of China [81100730, 81271102]
Odontoblasts and osteoblasts develop from multipotent craniofacial neural crest cells during tooth and jawbone development, but the mechanisms that specify and sustain their respective fates remain largely unknown. In this study we used early mouse molar and incisor tooth germs that possess distinct tooth-forming capability after dissociation and reaggregation in vitro to investigate the mechanism that sustains odontogenic fate of dental mesenchyme during tooth development. We found that after dissociation and reaggregation, incisor, but not molar, mesenchyme exhibits a strong osteogenic potency associated with robustly elevated beta-catenin signaling activity in a cell-autonomous manner, leading to failed tooth formation in the reaggregates. Application of FGF3 to incisor reaggregates inhibits beta-catenin signaling activity and rescues tooth formation. The lack of FGF retention on the cell surface of incisor mesenchyme appears to account for the differential osteogenic potency between incisor and molar, which can be further attributed to the differential expression of syndecan 1 and NDST genes. We further demonstrate that FGF signaling inhibits intracellular beta-catenin signaling by activating the PI3K/Akt pathway to regulate the subcellular localization of active GSK3 beta in dental mesenchymal cells. Our results reveal a novel function for FGF signaling in ensuring the proper fate of dental mesenchyme by regulating beta-catenin signaling activity during tooth development.
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