FAM20B-catalyzed glycosaminoglycans control murine tooth number by restricting FGFR2b signaling

Loading...
Thumbnail Image
Authors
Wu, Jingyi
Tian, Ye
Han, Lu
Liu, Chao
Sun, Tianyu
Li, Ling
Yu, Yanlei
Lamichhane, Bikash
D'Souza, Rena N.
Millar, Sarah E.
Issue Date
2020-07-14
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Research Projects
Organizational Units
Journal Issue
Alternative Title
Abstract
Background: The formation of supernumerary teeth is an excellent model for studying the molecular mechanisms that control stem/progenitor cell homeostasis needed to generate a renewable source of replacement cells and tissues. Although multiple growth factors and transcriptional factors have been associated with supernumerary tooth formation, the regulatory inputs of extracellular matrix in this regenerative process remains poorly understood. Results: In this study, we present evidence that disrupting glycosaminoglycans (GAGs) in the dental epithelium of mice by inactivating FAM20B, a xylose kinase essential for GAG assembly, leads to supernumerary tooth formation in a pattern reminiscent of replacement teeth. The dental epithelial GAGs confine murine tooth number by restricting the homeostasis of Sox2(+) dental epithelial stem/progenitor cells in a non-autonomous manner. FAM20B-catalyzed GAGs regulate the cell fate of dental lamina by restricting FGFR2b signaling at the initial stage of tooth development to maintain a subtle balance between the renewal and differentiation of Sox2(+) cells. At the later cap stage, WNT signaling functions as a relay cue to facilitate the supernumerary tooth formation. Conclusions: The novel mechanism we have characterized through which GAGs control the tooth number in mice may also be more broadly relevant for potentiating signaling interactions in other tissues during development and tissue homeostasis.
Description
BMC Biology, 18, 87
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
FAM20B-catalyzed glycosaminoglycans control murine tooth number by restricting FGFR2b signaling, J. Wu, Y. Tian, L. Han, C. Liu, T. Sun, L. Li, Y. Yu, B. Lamichhane, R. N. D’Souza, S. E. Millar, R. Krumlauf, D. M. Ornitz, J. Q. Feng, O. Klein, H. Zhao, F. Zhang, R. J. Linhardt, X. Wang, BMC Biology, 18, 87, 2020.
Publisher
Springer Nature
Journal
Volume
Issue
PubMed ID
DOI
ISSN
17417007
EISSN