Axon guidance cues in auditory development.
The innervation of the cochlear sensory epithelium is intricately organized, allowing the tonotopy established by the auditory hair cells to be maintained along the ascending auditory pathways. These auditory projections are patterned by several gene families that regulate neurite attraction and repulsion, known as axon guidance cues. In this review, the roles of various axon guidance molecules, including fibroblast growth factor, ephs, semaphorins, netrins and slits, are examined in light of their known contribution to auditory development. Additionally, morphogens are discussed in the context of their recently described influence on axonal pathfinding in other sensory systems. The elucidation of these various mechanisms may guide the development of therapies aimed at maximizing the connectivity of auditory neurons in the context of congenital or acquired sensorineural hearing loss, especially as pertains to cochlear implants. Further afield, improved understanding of the molecular processes which regulate innervation of the organ of Corti during normal development may prove useful in connecting regenerated hair cells to the central nervous system.