Adasooriya Dinuka, Jeong Ju-Kyung, Kyeong Minjae, Kan Shiqi, Kim Jiwoo, Cho Eui-Sic, Cho Sung-Won
Division of Anatomy and Developmental Biology, Department of Oral Biology, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, Korea.
Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Jeonbuk National University School of Dentistry, Jeonju, Korea.
Sci Rep. 2024 Jun 13;14(1):13633. doi: 10.1038/s41598-024-64340-w.
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.
Notum是Wnt/β-连环蛋白信号通路的直接靶点，在负反馈回路中作为Wnt抑制剂发挥关键作用。在牙齿中，已知Notum在成牙本质细胞中表达，并且在Notum基因缺失的小鼠中已报道有严重的牙本质缺陷和不规则的牙根。然而，Notum在牙齿早期发育中的精确表达模式以及Notum在牙冠和牙根形态中的作用仍不清楚。在本研究中，我们发现在牙齿发育过程中，Notum在原发性釉结（EK）、继发性EK和牙乳头中有新的表达。Notum基因缺失的小鼠表现出继发性EK增大，导致牙尖变宽、牙尖形态改变以及牙冠轮廓的凹陷减少。牙冠轮廓的这些改变导致颈舌长度缩短，从而在Notum基因缺失的小鼠中诱导牙根融合。总体而言，这些结果表明，由Wnt/Notum负反馈回路调节的继发性EK大小对牙齿形态发生过程中的牙冠和牙根形态有显著影响。
