Nogo-A modulates gene expression to fine-tune enamel development

Nogo-A is a major player in neural development and regeneration, and it is the target of several clinical trials. However, its functions outside the nervous system are mostly unknown. We observed that Nogo-A is expressed in dental epithelial cells, responsible for the formation of enamel, and we showed that the deletion of Nogo-A in transgenic mouse models leads to the formation of defective enamel. We observed that Nogo-A directly interacts with molecules important for gene expression regulation, and its deletion perturbs their cellular localization. As a result, Nogo-A deletion induces overexpression of genes involved in cell differentiation and enamel production. Mechanistically, we demonstrated that intracellular Nogo-A, and not cell surface Nogo-A, is responsible for gene expression modulation. Taken together, our results indicate a new role for Nogo-A as regulator of enamel formation and suggest a new possible cell-autonomous function in regulating gene expression and cell differentiation.