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 (DT), which induced selective HC ablation across vestibular organs. Both type I and type II HCs were lost following DT treatment. Type II HCs exhibited higher susceptibility to DT at lower doses, although this difference diminished as DT dose increased and overall HC survival declined. 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. Established a dose-dependent, HC-specific vestibular injury model enabling precise functional assessment. Revealed functional redundancy of vestibular HCs to balance maintenance. Identified type I HCs as essential for vestibular function, guiding targeted regenerative strategies. Using novel vestibular injury models, the authors identify functional redundancy in the system—balance requires only 30% of hair cells (HCs), and vestibulo-ocular reflexes require only 50%. Furthermore, they demonstrate that vestibular function has a critical dependence on the preservation of type I HCs, not merely on the total HC number.