Secondary induction and the development of tooth nerve supply

During embryogenesis, dental trigeminal axon navigation and patterning in the developing tooth take place in a highly spatio-temporally directed manner that is tightly linked to tooth morphogenesis and cell differentiation. Tooth formation is regulated by sequential and reciprocal tissue interactions between dental epithelium and neural crest-derived ectomesenchymal cells. This odontogenic secondary induction is mediated by signal molecules of different conserved families. Recent molecular and experimental data have provided evidence that local instructive signaling from the early odontogenic epithelium also controls dental axon navigation in the dental mesenchyme. In this review, we discuss recent molecular data regarding tooth formation and innervation and the putative role of the secondary induction in coordinating these two developmental processes. Importantly, because it has not yet been shown that the interactions that regulate tooth innervation include signaling to the dental epithelium and that they are reciprocal, it remains to be demonstrated that secondary induction controls the establishment of tooth nerve supply. Moreover, the key question of which molecule(s), if any, integrate tooth morphogenesis and the development of dental sensory trigeminal innervation remains to be answered.