Poster Sessions

DEV-11

Thomas Coate

T. Coate, B. Crenshaw, M. Kelley

Spiral Ganglion Neuron Pathfinding Requires Pou3f4 Activity in the Otic Mesenchyme during the Development of the Mouse Cochlea

During the formation of the cochlea, immature spiral ganglion neurons (SGNs) project axons through the otic mesenchyme to the developing sensory epithelium, where they innervate the inner and outer hair cells. Previously, it was demonstrated that the transcription factor Pou3f4 is expressed broadly in the cochlea during development, and that genetic removal of Pou3f4 leads to substantial hearing loss. However, the specific roles of Pou3f4 during inner ear formation are not fully understood. In the present study, we demonstrate that Pou3f4 expression is restricted to cells of the otic mesenchyme during SGN coalescence and axon outgrowth. SGNs from mice lacking Pou3f4 display multiple guidance defects, including incomplete axon fasciculation and misrouting of axons through the otic mesenchyme. Cross-sections of Pou3f4-deficient cochlea reveal that the relative density of neurons is unchanged, but there is substantial loss of glial cells that are normally apposed to the SGN soma. Interestingly, in mesenchyme/neuron explant cultures, Morpholino-mediated reduction of Pou3f4 leads to defects in neuron-neuron adhesion, whereas other aspects of their growth remain unaffected. These data suggest that Pou3f4 expression in the otic mesenchyme is necessary for expression of guidance cues that promote fasciculation of the SGNs during inner ear development.