Role of ephrin-A5 in the survival and connectivity of spiral ganglion neurons

Abstract

In mammals, degeneration of peripheral auditory neurons constitutes one of the prime causes of the sensorineural hearing loss. We believe that studying the developing auditory portion of the inner ear can provide important insights to mechanisms that would regulate regeneration after injury. In that context, our work has focused on a family of proteins, ephrins and Eph receptors, since they have been shown to have a dynamic influence in regulating developmental functions including axonal growth and guidance, synaptic formation and functions and neurogenesis. We have shown that ephrin-A5, EphA4 and EphA7 are expressed in the cell bodies of the spiral ganglion neurons, at different stages of the cochlear development. Ephrin-A5 also seems to be present in the hair cells of the organ of Corti. On the one hand, we demonstrated that activation of the signaling pathway by complexed ephrin-A5 in spiral ganglion explants reduced neuronal survival. On the other hand, an increase of neuronal survival was observed when blocking this mechanism of transduction by monomeric ephrin-A5. Taken together, these results suggest a role for ephrin/Eph signaling in regulating neuronal population generated in the spiral ganglion, especially during the post-natal period of the cochlear innervation