Elucidating the mechanisms of planar cell polarity-directed axon guidance in the peripheral auditory system

Our sense of hearing relies on proper wiring of the peripheral auditory system. The spiral ganglion neurons (SGNs) carry sound information from the inner and outer auditory hair cells in the cochlea to the hindbrain for further processing. Type II SGNs (SGNIIs) extend peripheral afferents into the cochlear epithelium, where they make a striking 90-degree turn toward the cochlear base and innervate multiple outer hair cells. The planar cell polarity (PCP) pathway has been shown to act non-autonomously in the cochlear epithelium to orchestrate this turning pattern, but the underlying mechanisms are unknown. In this dissertation, I explore potential downstream effectors of PCP signaling in SGNII afferent guidance. We identify Rac1, Nectin3, and PTK7 as novel regulators of SGNII afferent turning, and provide insight into how these proteins interact with the PCP pathway. This work also provides a basis for further investigation into how the mechanical and adhesive properties of the cochlear supporting cells may act as guidance cues for SGNII afferents. Overall, this work not only adds to our understanding of peripheral auditory system development, but also may have future translational implications for combating hearing loss.