Tissue interactions in the regulation of axon pathfinding during tooth morphogenesis

Like many other organs, the tooth develops as a result of the epithelial-mesenchymal interactions. In addition, the tooth is a well-defined peripheral target organ for sensory trigeminal nerves, which are required for the function and protection of the teeth. Dental trigeminal axon growth and patterning are tightly linked with advancing tooth morphogenesis and cell differentiation. This review summarizes recent findings on the regulation of dental axon pathfinding, which have provided evidence that the development of tooth trigeminal innervation is controlled by epithelial-mesenchymal interactions. The early dental epithelium possesses the information to instruct tooth nerve supply, and signals mediating these interactions are part of the signaling networks regulating tooth morphogenesis. Tissue interactions, thus, appear to provide a central mechanism of spatiotemporally orchestrating tooth formation and dental axon navigation and patterning.