The sensory nerve regulates stem cell homeostasis through Wnt5a signaling

Increasing evidence indicates that nerves play a significant role in regulating stem cell homeostasis and developmental processes. To explore the impact of nerves on epithelial stem cell homeostasis during tooth development, the regulation of the inferior alveolar nerve (IAN) and sensory nerves on stem cell homeostasis was investigated using a rat model of incisor development. Impaired mineralization, decreased enamel thickness, and fractured enamel rods of the incisor were observed after denervation. Transcriptome sequencing analysis and staining revealed that the IAN group had decreased expression of Wnt5a and enamel-related genes kallikrein-4, odontogenic ameloblast-associated protein, and amelotin. The decreased expression of Wnt5a in ameloblasts was coupled with the downregulation of calcium ion-related calmodulin kinase II. These results implicate that the sensory nerves, as the most critical component of the inferior alveolar nerve, are essential in stem cell homeostasis for enamel mineralization and development.