Abstract
Hundreds of millions of people worldwide have disabling hearing loss or imbalance. A major cause of these impairments is sensory hair cell loss from loud sounds, ototoxic drugs, and aging. Birds, fish, and amphibians recover hearing and vestibular function after hair cell loss, as neighboring supporting cells retain a lifelong capacity to divide and differentiate into replacement hair cells. In mammals, supporting cell plasticity declines sharply during maturation. Thus, major research goals are to define the mechanisms of hair cell replacement in nonmammals and identify unique maturational changes in mammalian supporting cells that restrict these regenerative mechanisms. After the first report of self-repair in the chicken basilar papilla described pronounced shape changes of supporting cells within acoustic lesions, it was hypothesized that mechanical forces associated with that shape change trigger regenerative proliferation. Subsequent investigations found that age-related changes in the intercellular junctions of mammalian supporting cells strongly correlate with reductions in cellular shape change and supporting cell proliferation, while supporting cells in chickens do not change with age and retain proliferative capacity. Mammalian supporting cell junctions are bracketed by exceptionally thick circumferential F-actin bands and express high levels of E-cadherin, which is barely detectable in most nonmammalian supporting cells. This chapter outlines the hypothesis that these specialized junctions of mammalian supporting cells impede changes in tension that occur in nonmammalian supporting cells, reviews findings implicating the mechano-responsive Hippo and Wnt pathways in regenerative proliferation, and highlights unanswered questions regarding the role of epithelial mechanics in hair cell regeneration.
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The authors thank Jennifer Stone, Mark Warchol, and Art Popper for helpful comments.
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Mark A. Rudolf declares that he has no conflict of interest.
Jeffrey T. Corwin declares that he has no conflict of interest.
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Rudolf, M.A., Corwin, J.T. (2023). Cell Junctions and the Mechanics of Hair Cell Regeneration. In: Warchol, M.E., Stone, J.S., Coffin, A.B., Popper, A.N., Fay, R.R. (eds) Hair Cell Regeneration. Springer Handbook of Auditory Research, vol 75. Springer, Cham. https://doi.org/10.1007/978-3-031-20661-0_3
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