Vestibular Hair Cell Redundancy and the Critical Requirement of Type I Cells for Balance Maintenance

Vestibular hair cells (HCs) are sensory mechanotransducers essential for balance and spatial orientation, yet the relative contributions of HC number and subtype to vestibular function remain unresolved. Here, we developed a dose-dependent injury model in adult Pou4f3DTR mice by administering diphtheria toxin, which induced selective HC ablation across vestibular organs. Functional analyses revealed that mice retaining ~30% of vestibular HCs—with preserved subtype proportions and neural innervation—exhibited normal balance, while ~50% residual HCs were sufficient to maintain intact vestibulo-ocular reflexes. To elucidate subtype-specific roles, we employed two type I HC–deficient models: 3,3′-iminodipropionitrile-induced injury and Gfi1Cre/Atoh1-OE mice. Comparative analyses revealed that type I HCs were essential for vestibular function. Together, these findings establish a reliable injury model, demonstrate functional redundancy within vestibular HCs, and underscore the critical role of type I HCs. These insights suggest that efforts to restore vestibular function through HC regeneration should prioritize generating functional type I HCs, not merely increasing the total HC count.