As the sole conduit for sound information from the inner ear to the central auditory system, spiral ganglion neurons are important therapeutic targets for the treatment of deafness. Indeed, the promise of hair cell regeneration is limited by whether new hair cells can be properly innervated by spiral ganglion neurons. Thus, efforts to stimulate hair cell regeneration must be coordinated with efforts to induce neurite outgrowth in surviving neurons or to replace lost neurons with stem cells. The long term goal of the work in my laboratory is to dissect the genetic basis of auditory circuit assembly, focusing on the molecules that drive auditory-specific programs of differentiation in spiral ganglion neurons. Towards this end, we have developed genetic tools that allow us to visualize the pattern of innervation in the cochlea at any stage of development (see figure). We have also created a catalog of genes that are uniquely expressed in spiral ganglion neurons but not in the closely related vestibular ganglion neurons, which mediate the sense of balance. Currently, we are elucidating functions for these auditory-specific genes, both by analyzing available mutant mice and by developing a new technique for performing a forward genetic screen. Together, these studies will deepen our understanding of the normal developmental program for spiral ganglion neurons, information that is critical for future efforts to engineer naïve stem cells to re-wire the cochlea as a treatment for deafness.
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