Fig. 9

Hypothetic mechanism by which GAGs restrict tooth number in mice. A At the initial stage of tooth development, FAM20B-catalyzed GAGs commit the cell fate of dental epithelium by restricting the diffusion gradient of FGF10 from dental mesenchyme into dental epithelium in the process of activating FGFR2b signaling. B At late cap stage, overactivated WNT signaling plays as the relay cue to facilitate the supernumerary tooth formation. C Under normal condition, FAM20B phosphorylates the xylose in the linkage region of GAGs, which is essential for GAG assembly. GAGs in the ECM and on the cell surface interact with FGF10 ligands to shape a restricted diffusion gradient, which is essential for controlling the FGFR2b-mediated signaling balance between the renewal and differentiation of Sox2(+) stem/progenitor cells in the dental epithelium. D Inactivation of Fam20B in the dental epithelium leads to GAG deficiency, which facilitates FGF10 diffusion and access to FGFR2b. The upregulated FGFR2b signaling overweighs the renewal of Sox2(+) cells in the dental epithelium, leading to replacement-like tooth formation in monophyodont mice