Early neuronal processes interact with glia to establish a scaffold for orderly innervation of the cochlea

Summary Although the basic principles of axon guidance are well established, it remains unclear how axons navigate with high fidelity through the complex cellular terrains that are encountered in vivo . To learn more about the cellular strategies underlying axon guidance in vivo , we analyzed the developing cochlea, where spiral ganglion neurons extend processes through a heterogeneous cellular environment to form tonotopically ordered connections with hair cells. Here, we show that the earliest processes are closely associated with a population of glia that grow ahead of them. By analyzing single cell morphology and imaging the real time behavior of neuronal processes and glia in embryonic cochleae, we show that spiral ganglion neurons employ different mechanisms depending on their position in the ganglion. Additionally, the pattern of outgrowth varied locally, with evidence for both glia-guided growth and fasciculation along a neuronal scaffold. These findings suggest a tiered mechanism for reliable axon guidance.