牙根是牙齿维持稳固和行使咀嚼功能的重要部分。牙根发育异常是牙齿发育异常的一种，常导致牙齿早期丧失，影响咀嚼功能和颌面部发育。与牙冠发育中的信号网络被广泛研究和详尽阐明不同，牙根发育的系统性研究匮乏，牙根发育的调控机制知之甚少。在牙根发育过程中，Wnt10a持续地特异性表达在紧邻新生牙本质的间充质细胞内。我们在前期研究中创新性地构建了全敲除Wnt10a基因的EIIa-Cre;Wnt10afl/fl，该小鼠的下颌磨牙牙根存在明显的发育缺陷，提示我们牙源间充质特异性表达Wnt10a在牙根发育中存在着重要的作用。为深入研究调控机制，本项目拟构建在牙根前体细胞、牙间充质细胞和牙上皮细胞特异性敲除Wnt10a基因的三种条件性基因敲除小鼠模型，从转录组、甲基化和非编码RNA水平上阐明并验证牙源间充质特异性表达Wnt10a在牙根发育中的作用和调控机制，寻找相关靶点并探讨其在牙齿再生治疗中的意义与可行性。

Root is an important part of a tooth, which maintain the stabilization and perform the physiological functions of tooth. The developmental defect of tooth root is a type of tooth agenesis, which lead to early loss of tooth, impair the masticatory function, craniofacial development and oral health. The process of tooth development, the critical molecules involved in tooth crown formation and its reciprocal induction events have been addressed by multiple studies in recent years. However, the molecular regulation of tooth root development is rare to study and remains unclear. Wnt10a is specifically expressed in the dental mesenchymal cells lining the inner dentin surface during tooth root development. In previous study, we developed a new mouse strain, Wnt10afl/fl, and generated EIIa-Cre;Wnt10afl/fl mice, which completely knock out Wnt10a in all kinds of cells. We found that the molar root showed severe developmental defect in EIIa-Cre;Wnt10afl/fl mice, suggesting that mesenchymal cell specific expression of Wnt10a plays crucial role during tooth root development. In this study, we plan to generate three different Wnt10a conditional knockout mice model, including Gli1-CreERT2;Wnt10afl/fl mice, which targeting the tooth root progenitor cells; Wnt1-Cre;Wnt10afl/fl mice, which targeting the dental mesenchymal cells, and K14-Cre;Wnt10afl/fl mice, which targeting the dental epithelial cells. We plan to perform a series of experiments, to illustrate the molecular regulatory mechanism of mesenchymal cell specific expressed Wnt10a during tooth root development from the transcriptome, methylation, and non-coding RNA level. The results of our study will provide useful information for therapeutic strategy for the congenital tooth root defect and tooth regeneration.