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

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 by in situ hybridization that ephrin-A5 is expressed in a small proportion of the spiral ganglion neurons, at different stages of the cochlear development. Most of them are located on the edge of the spiral ganglion. We demonstrated that the amount of neurons falls of more than 50% in P5 ephrin-A5 knockout mice as compared to wild type. Moreover, the numbers of TUNEL and active caspase-3 positive cells in the spiral ganglion are significantly increased at P0 when ephrin-A5 is deleted. Finally, we established that lack of ephrin-A5 leads to a defective inner hair cell innervation. Taken together, these results suggest a role for ephrin-A5 in regulating survival of auditory neurons and establishment of connectivity to sensory hair cells during development.