The molecular basis of making spiral ganglion neurons and connecting them to hair cells of the organ of Corti.

The bipolar spiral ganglion neurons apparently delaminate from the growing cochlear duct and migrate to Rosenthal's canal. They project radial fibers to innervate the organ of Corti (type I neurons to inner hair cells, type II neurons to outer hair cells) and also project tonotopically to the cochlear nuclei. The early differentiation of these neurons requires transcription factors to regulate migration, pathfinding and survival. Neurog1 null mice lack formation of neurons. Neurod1 null mice show massive neuronal death combined with aberrant central and peripheral projections. Prox1 protein is necessary for proper type II neuron process navigation, which is also affected by the neurotrophins Bdnf and Ntf3. Neurotrophin null mutants show specific patterns of neuronal loss along the cochlea but remaining neurons compensate by expanding their target area. All neurotrophin mutants have reduced radial fiber growth proportional to the degree of loss of neurotrophin alleles. This suggests a simple dose response effect of neurotrophin concentration. Keeping overall concentration constant, but misexpressing one neurotrophin under regulatory control of another one results in exuberant fiber growth not only of vestibular fibers to the cochlea but also of spiral ganglion neurons to outer hair cells suggesting different effectiveness of neurotrophins for spiral ganglion neurite growth. Finally, we report here for the first time that losing all neurons in double null mutants affects extension of the cochlear duct and leads to formation of extra rows of outer hair cells in the apex, possibly by disrupting the interaction of the spiral ganglion with the elongating cochlea.