Study of non- and mammalian inner ear hair cell regeneration by time lapse imaging

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The inability for inner ear self-regeneration in mammals is the main reason for incurability of hearing loss and balance disorders. In contrast, non-mammalian vertebrates regenerate hair cells throughout life. This ability is mediated by resident stem cells, likely vestibular and cochlear supporting cells via two different mechanisms: trans-differentiation and proliferation. The underlying signaling pathways for non-mammalian hair cell regeneration are unknown. It remains unclear whether the mammalian inability for hair cell regeneration results from the lack of regenerative signals or the inability to respond to regeneration-inducing signals. I propose to develop an in vitro assay system for hair cell regeneration by time lapse imaging of regenerating chicken vestibular sensory epithelia after inducing hair cell loss. I will determine whether all utricle supporting cells or distinct stem cell populations serve as somatic stem cells. I will discriminate characteristics, cell fates and morphological changes between the two mechanisms. Further, I plan to manipulate cells that are capable of regenerating hair cells by gain- and loss-of-function approaches. In addition, I intend to generate mosaics of murine and chicken hair and supporting cells. I propose to track the fate of individual murine supporting cells to investigate whether proximity or direct contact with regenerating chicken supporting cells affects their regenerative capacity. This proposal addresses a fundamental question of inner ear biology and successful completion could lead to the development of novel approaches for curing hearing loss.