The Hippo signaling pathway is a key regulator of tissue development and regeneration. Activation of the Hippo pathway leads to nuclear translocation of the YAP1 transcriptional coactivator, resulting in changes in gene expression and cell cycle entry. Recent studies have demonstrated the nuclear translocation of YAP1 during the development of the sensory organs of the inner ear, but the possible role of YAP1 in sensory regeneration of the inner ear is unclear. The present study characterized the cellular localization of YAP1 in the utricles of mice and chicks, both under normal conditions and after HC injury. During neonatal development, YAP1 expression was observed in the cytoplasm of supporting cells, and was transiently expressed in the cytoplasm of some differentiating hair cells. We also observed temporary nuclear translocation of YAP1 in supporting cells of the mouse utricle after short periods in organotypic culture. However, little or no nuclear translocation of YAP1 was observed in the utricles of neonatal or mature mice after ototoxic injury. In contrast, substantial YAP1 nuclear translocation was observed in the chicken utricle after streptomycin treatment in vitro and in vivo. Together, these data suggest that differences in YAP1 signaling may partially account for the differing regenerative abilities of the avian vs. mammalian inner ear.

The Hippo pathway is an evolutionarily conserved signaling pathway involved in regulating organ size, development, homeostasis and regeneration [1][2][3][4] . YAP1 is a transcriptional coactivator and the primary effector of Hippo signaling. Upstream activation of the Hippo pathway leads to nuclear translocation of YAP1, which then evokes changes in gene expression and cell cycle entry 5 . A prior study has demonstrated nuclear translocation of YAP1 in the supporting cells of the developing utricle 6 , but the possible role of YAP1 in hair cell regeneration is unclear. The present study characterizes the cellular localization of YAP1 in the utricles of mice and chicks, both under normal conditions and after hair cell injury. During neonatal development of the mouse utricle, YAP1 expression was observed in the cytoplasm ofsupporting cells, and was also transiently expressed in the cytoplasm of hair cells. We also observed temporary nuclear translocation of YAP1 in supporting cells of the mouse utricle at short time periods after placement in organotypic culture. However, little or no nuclear translocation of YAP1 was observed after injury to the utricles of neonatal or mature mice. In contrast, a significant degree of YAP1 nuclear translocation was observed in the chicken utricle after streptomycin-induced hair cell damage in vitro and in vivo. Together, these data suggest that differences in YAP1 signaling may be partly responsible for the distinct regenerative abilities of the avian vs. mammalian inner ear.

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