PDF(Pubmed)
Abstract：
Notum is a direct target of Wnt/β-catenin signaling and plays a crucial role as a Wnt inhibitor within a negative feedback loop. In the tooth, Notum is known to be expressed in odontoblasts, and severe dentin defects and irregular tooth roots have been reported in Notum-deficient mice. However, the precise expression pattern of Notum in early tooth development, and the role of Notum in crown and root patterns remain elusive. In the present study, we identified a novel Notum expression in primary enamel knot (EK), secondary EKs, and dental papilla during tooth development. Notum-deficient mice exhibited enlarged secondary EKs, resulting in broader cusp tips, altered cusp patterns, and reduced concavity in crown outline. These alterations in crown outline led to a reduction in cervical tongue length, thereby inducing root fusion in Notum-deficient mice. Overall, these results suggest that the secondary EK size, regulated by the Wnt/Notum negative feedback loop, has a significant impact on the patterns of crown and root during tooth morphogenesis.
摘要：
Notum是Wnt/β-连环蛋白信号传导的直接靶标,并且在负反馈回路中作为Wnt抑制剂发挥关键作用。在牙齿上，已知Notum在成牙本质细胞中表达，在Notum缺陷小鼠中已经报道了严重的牙本质缺陷和不规则的牙根。然而,Notum在早期牙齿发育中的精确表达模式，Notum在冠状和根部模式中的作用仍然难以捉摸。在本研究中,我们确定了一个新的Notum表达在初级釉质结（EK），次要EK,和牙齿发育过程中的牙乳头。Notum缺陷小鼠表现出增大的继发性EK，导致更广泛的尖端，改变了尖点模式，并减少表冠轮廓的凹度。这些牙冠轮廓的改变导致颈舌长度的减少，从而在Notum缺陷小鼠中诱导根融合。总的来说,这些结果表明，次级EK大小，由Wnt/Notum负反馈回路调节，在牙齿形态发生过程中对牙冠和牙根的模式有重大影响。
