Eps8 regulates cochlear and vestibular hair cell development

Deletion of Epidermal growth factor receptor pathway substrate 8 (Eps8), a gene involved in actin remodeling, causes deafness in mice. Cochlear inner hair cells from Eps8-knockout (KO) mice have abnormally short stereocilia and fail to acquire their mature array of basolateral voltage-gated K+ channels. Intriguingly, Eps8-KO mice show no vestibular deficits despite the fact that Eps8 is also expressed in vestibular hair cells. Since vestibular deficits are sometimes centrally compensated, we have investigated if vestibular Type I and Type II hair cells in Eps8-KO mice were also affected by Eps8 deletion. We found that, like cochlear hair cells, Eps8-KO vestibular hair cells have significantly shorter than normal stereocilia. However, KO Type I and Type II hair cells expressed a normal pattern of basolateral voltage-dependent ion channels. Consistent with this finding, the voltage response of KO vestibular hair cells to injected sinusoidal currents, which were used to mimic the mechanoelectrical transducer current, was analogous to that found in WT hair cells. We conclude that the absence of Eps8 has a weaker effect in vestibular hair cells compared to cochlear hair cells, since it affects the stereocilia length but not the voltage-dependent properties. This difference, together with the possible compensation for the shorter stereocilia by the cupula, may explain the absence of obvious vestibular deficits in Eps8-KO mice.