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. 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. 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.

中文翻译：

---

FAM20B催化的糖胺聚糖通过限制FGFR2b信号传导来控制鼠齿数。

多余牙齿的形成是研究控制干/祖细胞稳态以生成替代细胞和组织的可再生来源所需的分子机制的绝佳模型。尽管多种生长因子和转录因子已经与多余的牙齿形成相关联，但是在这种再生过程中细胞外基质的调控输入仍然知之甚少。在这项研究中，我们提供的证据表明，通过灭活GAM组装所必需的木糖激酶FAM20B破坏小鼠牙齿上皮中的糖胺聚糖（GAGs），会导致多余牙齿的形成，令人联想到替代牙齿。牙齿上皮GAG通过以非自主方式限制Sox2（+）牙齿上皮干/祖细胞的稳态来限制鼠齿数。FAM20B催化的GAG通过限制牙齿发育初期的FGFR2b信号传导来维持牙齿的层状，以维持Sox2（+）细胞的更新和分化之间的微妙平衡。在下盖阶段，WNT信号作为中继提示以促进多余牙齿的形成。我们所表征的新机制，通过GAG控制小鼠的牙齿数量，在发育和组织动态平衡过程中可能还与增强其他组织中的信号传导相互作用更为广泛相关。FAM20B催化的GAG通过限制牙齿发育初期的FGFR2b信号传导来维持牙齿的层状，以维持Sox2（+）细胞的更新和分化之间的微妙平衡。在下盖阶段，WNT信号作为中继提示来促进多余牙齿的形成。我们所表征的新机制，通过GAG控制小鼠的牙齿数量，在发育和组织动态平衡过程中可能还与增强其他组织中的信号传导相互作用更为广泛相关。FAM20B催化的GAG通过限制牙齿发育初期的FGFR2b信号传导来维持牙齿的层状，以维持Sox2（+）细胞的更新和分化之间的微妙平衡。在下盖阶段，WNT信号作为中继提示来促进多余牙齿的形成。我们所表征的新机制，通过GAG控制小鼠的牙齿数量，在发育和组织动态平衡过程中可能还与增强其他组织中的信号传导相互作用更为广泛相关。