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Stiffening of Circumferential F-Actin Bands Correlates With Regenerative Failure and May Act as a Biomechanical Brake in the Mammalian Inner Ear

The loss of inner ear hair cells causes permanent hearing and balance deficits in humans and other mammals, but non-mammals recover after supporting cells (SCs) divide and replace hair cells. The proliferative capacity of mammalian SCs declines as exceptionally thick circumferential F-actin bands de...

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Autores principales: Rudolf, Mark A., Andreeva, Anna, Kim, Christina E., DeNovio, Anthony C.-J., Koshar, Antoan N., Baker, Wendy, Cartagena-Rivera, Alexander X., Corwin, Jeffrey T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114303/
https://www.ncbi.nlm.nih.gov/pubmed/35602553
http://dx.doi.org/10.3389/fncel.2022.859882
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author Rudolf, Mark A.
Andreeva, Anna
Kim, Christina E.
DeNovio, Anthony C.-J.
Koshar, Antoan N.
Baker, Wendy
Cartagena-Rivera, Alexander X.
Corwin, Jeffrey T.
author_facet Rudolf, Mark A.
Andreeva, Anna
Kim, Christina E.
DeNovio, Anthony C.-J.
Koshar, Antoan N.
Baker, Wendy
Cartagena-Rivera, Alexander X.
Corwin, Jeffrey T.
author_sort Rudolf, Mark A.
collection PubMed
description The loss of inner ear hair cells causes permanent hearing and balance deficits in humans and other mammals, but non-mammals recover after supporting cells (SCs) divide and replace hair cells. The proliferative capacity of mammalian SCs declines as exceptionally thick circumferential F-actin bands develop at their adherens junctions. We hypothesized that the reinforced junctions were limiting regenerative responses of mammalian SCs by impeding changes in cell shape and epithelial tension. Using micropipette aspiration and atomic force microscopy, we measured mechanical properties of utricles from mice and chickens. Our data show that the epithelial surface of the mouse utricle stiffens significantly during postnatal maturation. This stiffening correlates with and is dependent on the postnatal accumulation of F-actin and the cross-linker Alpha-Actinin-4 at SC-SC junctions. In chicken utricles, where SCs lack junctional reinforcement, the epithelial surface remains compliant. There, SCs undergo oriented cell divisions and their apical surfaces progressively elongate throughout development, consistent with anisotropic intraepithelial tension. In chicken utricles, inhibition of actomyosin contractility led to drastic SC shape change and epithelial buckling, but neither occurred in mouse utricles. These findings suggest that species differences in the capacity for hair cell regeneration may be attributable in part to the differences in the stiffness and contractility of the actin cytoskeletal elements that reinforce adherens junctions and participate in regulation of the cell cycle.
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spelling pubmed-91143032022-05-19 Stiffening of Circumferential F-Actin Bands Correlates With Regenerative Failure and May Act as a Biomechanical Brake in the Mammalian Inner Ear Rudolf, Mark A. Andreeva, Anna Kim, Christina E. DeNovio, Anthony C.-J. Koshar, Antoan N. Baker, Wendy Cartagena-Rivera, Alexander X. Corwin, Jeffrey T. Front Cell Neurosci Neuroscience The loss of inner ear hair cells causes permanent hearing and balance deficits in humans and other mammals, but non-mammals recover after supporting cells (SCs) divide and replace hair cells. The proliferative capacity of mammalian SCs declines as exceptionally thick circumferential F-actin bands develop at their adherens junctions. We hypothesized that the reinforced junctions were limiting regenerative responses of mammalian SCs by impeding changes in cell shape and epithelial tension. Using micropipette aspiration and atomic force microscopy, we measured mechanical properties of utricles from mice and chickens. Our data show that the epithelial surface of the mouse utricle stiffens significantly during postnatal maturation. This stiffening correlates with and is dependent on the postnatal accumulation of F-actin and the cross-linker Alpha-Actinin-4 at SC-SC junctions. In chicken utricles, where SCs lack junctional reinforcement, the epithelial surface remains compliant. There, SCs undergo oriented cell divisions and their apical surfaces progressively elongate throughout development, consistent with anisotropic intraepithelial tension. In chicken utricles, inhibition of actomyosin contractility led to drastic SC shape change and epithelial buckling, but neither occurred in mouse utricles. These findings suggest that species differences in the capacity for hair cell regeneration may be attributable in part to the differences in the stiffness and contractility of the actin cytoskeletal elements that reinforce adherens junctions and participate in regulation of the cell cycle. Frontiers Media S.A. 2022-05-04 /pmc/articles/PMC9114303/ /pubmed/35602553 http://dx.doi.org/10.3389/fncel.2022.859882 Text en Copyright © 2022 Rudolf, Andreeva, Kim, DeNovio, Koshar, Baker, Cartagena-Rivera and Corwin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Rudolf, Mark A.
Andreeva, Anna
Kim, Christina E.
DeNovio, Anthony C.-J.
Koshar, Antoan N.
Baker, Wendy
Cartagena-Rivera, Alexander X.
Corwin, Jeffrey T.
Stiffening of Circumferential F-Actin Bands Correlates With Regenerative Failure and May Act as a Biomechanical Brake in the Mammalian Inner Ear
title Stiffening of Circumferential F-Actin Bands Correlates With Regenerative Failure and May Act as a Biomechanical Brake in the Mammalian Inner Ear
title_full Stiffening of Circumferential F-Actin Bands Correlates With Regenerative Failure and May Act as a Biomechanical Brake in the Mammalian Inner Ear
title_fullStr Stiffening of Circumferential F-Actin Bands Correlates With Regenerative Failure and May Act as a Biomechanical Brake in the Mammalian Inner Ear
title_full_unstemmed Stiffening of Circumferential F-Actin Bands Correlates With Regenerative Failure and May Act as a Biomechanical Brake in the Mammalian Inner Ear
title_short Stiffening of Circumferential F-Actin Bands Correlates With Regenerative Failure and May Act as a Biomechanical Brake in the Mammalian Inner Ear
title_sort stiffening of circumferential f-actin bands correlates with regenerative failure and may act as a biomechanical brake in the mammalian inner ear
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114303/
https://www.ncbi.nlm.nih.gov/pubmed/35602553
http://dx.doi.org/10.3389/fncel.2022.859882
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