Tooth root morphogenesis involves two biological processes, root elongation and dentinogenesis, which are guaranteed by downgrowth of Hertwig’s epithelial root sheath (HERS) and normal odontoblast differentiation. Ubiquitin-dependent protein degradation has been reported to precisely regulate various physiological processes, while its role in tooth development is still elusive. Here we show ubiquitin-specific protease 34 (USP34) plays a pivotal role in root formation. Deletion of Usp34 in dental mesenchymal cells leads to short root anomaly, characterized by truncated roots and thin root dentin. The USP34-deficient dental pulp cells (DPCs) exhibit decreased odontogenic differentiation with downregulation of nuclear factor I/C (NFIC). Overexpression of NFIC partially restores the impaired odontogenic potential of DPCs. These findings indicate that USP34-dependent deubiquitination is critical for root morphogenesis by stabilizing NFIC.

牙根形态发生涉及两个生物过程，即根伸长和牙本质发生，这是由赫特维希上皮根鞘（HERS）向下生长和正常成牙本质细胞分化保证的。据报道，泛素依赖性蛋白质降解可以精确调节各种生理过程，但其在牙齿发育中的作用仍然难以捉摸。在这里，我们展示了泛素特异性蛋白酶 34 (USP34) 在根形成中发挥着关键作用。牙间充质细胞中Usp34的缺失会导致短牙根异常，其特征是牙根截短和根牙本质薄。 USP34缺陷的牙髓细胞 (DPC) 表现出牙源性分化减少，核因子 I/C (NFIC) 下调。 NFIC 的过度表达可部分恢复 DPC 受损的成牙潜力。这些发现表明，USP34 依赖性去泛素化通过稳定 NFIC 对根形态发生至关重要。