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During development the afferent neurons of the inner ear make precise wiring decisions in the hindbrain reflective of their topographic distribution in the periphery. This is critical for the formation of sensory maps capable of faithfully processing both auditory and vestibular input. Disorganized central projections of inner ear afferents in  Fzd3  null mice indicate Wnt/PCP signaling is involved in this process and ear transplantation in  Xenopus  indicates that  Fzd3  is necessary in the ear but not the hindbrain for proper afferent navigation. However, it remains unclear in which cell type of the inner ear  Fzd3  expression is influencing the guidance of inner ear afferents to their proper synaptic targets in the hindbrain. We utilized  Atoh1-cre  and  Neurod1-cre  mouse lines to conditionally knockout  Fzd3  within the mechanosensory hair cells of the organ of Corti and within the inner ear afferents, respectively. Following conditional deletion of  Fzd3  within the hair cells, the central topographic distribution of inner ear afferents was maintained with no gross morphological defects. In contrast, conditional deletion of  Fzd3  within inner ear afferents leads to central pathfinding defects of both cochlear and vestibular afferents. Here, we show that  Fzd3  is acting in a cell autonomous manner within inner ear afferents to regulate central pathfinding within the hindbrain.

Fzd3 Expression Within Inner Ear Afferent Neurons Is Necessary for Central Pathfinding