上皮Wnt10a通过Gsk3β和Hedgehog信号通路调控牙根分叉形成的机制

牙根是牙齿行使生理功能的基础，阐明牙根的生长发育机制是实现组织再生的前提，但是目前对于牙根发育的分子调控机制知之甚少。课题组在前期研究中证实牙胚上皮条件性敲除Wnt10a基因（K14-Cre;Wnt10afl/fl）会导致牛牙症，成功构建了与人类WNT10A双等位基因突变患者的牙根发育缺陷一致的疾病小鼠模型。通过RNA-Seq发现了上皮敲除Wnt10a后牙胚表达基因谱的变化，其中Gsk3β、Wnt和Hh信号通路的变化尤为值得关注。本项目将继续利用该牙根缺陷小鼠模型，通过RNAscope、表型复制和表型逆转等实验，深入研究牙胚上皮内Wnt10a-Gsk3β(-Hh)信号级联促进牙冠中部HERS上皮增殖形成舌头样凸起封闭髓室底，继而决定根分叉及牙根数目的机制。在器官水平进一步阐明牙根形态发生的调控机制，寻找相关靶点并探讨其在组织工程再生的生物牙根改良中的意义与可行性。

The tooth root is an integral, functionally important part of our dentition, and the mechanism of root growth and development is the basis of tissue regeneration, however, little is known about the molecular mechanism of root development. In previous studies, we revealed that conditional knockout Wnt10a gene in dental epithelium (K14-Cre;Wnt10afl/fl) resulted in taurodontism, generated a tooth root defect mouse model which was phenotypically consistent with bi-allelic WNT10A loss-of-function mutation related disease in human successfully. Using RNA-Seq, we found the expression changes of the genes in tooth germ after epithelial Wnt10a was knockout. The changes of expression in Gsk3β, Wnt and Hh signaling pathways are particularly noteworthy. The aim of this project is to elucidate the mechanism of epithelial Wnt10a-Gsk3β(-Hh) signaling cascade controls tooth root furcation formation and the number of roots through experiments such as RNAscope, phenotypical replication and phenotypical rescue. We are aiming to further elucidate the regulation mechanism of root morphogenesis, investigate the significance and feasibility of the mechanism in optimizing tissue engineering bio-root.