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

BMC Biology

Chao Liu¹  Jian Q. Feng¹  Bikash Lamichhane¹  Lu Han¹  Xiaofang Wang¹  Ye Tian¹  Hu Zhao¹  Yanlei Yu²  Robert J. Linhardt²  Fuming Zhang²  Sarah E. Millar³  Ling Li⁴  David M. Ornitz⁴  Ophir Klein⁵  Rena N. D’Souza⁶  Tianyu Sun⁷  Jingyi Wu⁷  Robb Krumlauf⁸ 

[1] Department of Biomedical Sciences, Texas A&M University College of Dentistry;Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute;Department of Dermatology, Perelman School of Medicine, University of Pennsylvania;Department of Developmental Biology, Washington University School of Medicine;Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco;School of Dentistry, University of Utah;Southern Medical University Hospital of Stomatology;Stowers Institute for Medical Research;

关键词: Glycosaminoglycan;    Proteoglycan;    Fam20B;    Kinase;    Supernumerary teeth;    Tooth renewal;   

DOI  :  10.1186/s12915-020-00813-4

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown