An important aspect for axonal regeneration in the adult is appropriate axonal guidance. We have shown in our previous work that treatment with an RARβ agonist leads to axonal regeneration and functional recovery in a rat model of sensory root avulsion (Goncalves et al., 2015). Here we identify a novel mechanism by which neuronal RARβ activation results in the endogenous synthesis of RA which is released in association with exosomes and acts as a positive cue to axonal/neurite outgrowth.