Functional roles of Nogo-A in tooth innervation

Tooth innervation is unique as it is composed by a dense neuronal network of highly specialized nociceptors. Innervation is essential for tooth homeostasis and the protection and regeneration of dental tissues upon injury. It is thus important to understand the physiological functions of molecules involved in tooth innervation, in order to translate this knowledge to the dental clinics. Nogo-A is a molecule regulating central nervous system (CNS) innervation, by affecting the migration, outgrowth and branching of neurons during embryonic development. In adulthood, Nogo-A contributes to neuronal network stability, while upon CNS injury it inhibits neuronal axon regeneration. These properties of Nogo-A have been and are still exploited in clinical trials for the treatment of CNS injuries. However, although the functions of Nogo-A in CNS are well-known, its role in tooth innervation remains largely unknown. In this study, we aim to uncover the roles of Nogo-A in the establishment of tooth innervation, in tooth homeostasis and regeneration. We used immunostaining and in situ hybridization analyses to describe Nogo-A expression in the trigeminal neurons and dental tissues in mice. In addition, morphological, genetic and pharmacological ablation studies were performed to demonstrate the ability of Nogo-A to regulate tooth innervation. Our results showed that Nogo-A is expressed in the trigeminal ganglion and dental tissues from the earliest developmental stages, and that this expression persisted until adulthood. In the trigeminal ganglion, Nogo-A is localised both in the cell bodies and the projecting to the teeth nerve fibres. Genetic or pharmacological ablation of Nogo-A affected the branching and compactness of the dental pulp neuronal network, while in the trigeminal ganglia this ablation affected the neuronal projections pattern. Taken together, our findings indicate that Nogo-A is a regulator of tooth innervation. The ongoing transcriptomic analyses will enable further unravelling the importance of Nogo-A in tooth innervation.