Atoh1 Directs Regeneration and Functional Recovery of the Mature Mouse Vestibular System
Summary: Utricular hair cells (HCs) are mechanoreceptors required for vestibular function. After damage, regeneration of mammalian utricular HCs is limited and regenerated HCs appear immature. Thus, loss of vestibular function is presumed irreversible. Here, we found partial HC replacement and funct...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719307946 |
| _version_ | 1819061453748961280 |
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| author | Zahra N. Sayyid Tian Wang Leon Chen Sherri M. Jones Alan G. Cheng |
| author_facet | Zahra N. Sayyid Tian Wang Leon Chen Sherri M. Jones Alan G. Cheng |
| author_sort | Zahra N. Sayyid |
| collection | DOAJ |
| description | Summary: Utricular hair cells (HCs) are mechanoreceptors required for vestibular function. After damage, regeneration of mammalian utricular HCs is limited and regenerated HCs appear immature. Thus, loss of vestibular function is presumed irreversible. Here, we found partial HC replacement and functional recovery in the mature mouse utricle, both enhanced by overexpressing the transcription factor Atoh1. Following damage, long-term fate mapping revealed that support cells non-mitotically and modestly regenerated HCs displaying no or immature bundles. By contrast, Atoh1 overexpression stimulated proliferation and widespread regeneration of HCs exhibiting elongated bundles, patent mechanotransduction channels, and synaptic connections. Finally, although damage without Atoh1 overexpression failed to initiate or sustain a spontaneous functional recovery, Atoh1 overexpression significantly enhanced both the degree and percentage of animals exhibiting sustained functional recovery. Therefore, the mature, damaged utricle has an Atoh1-responsive regenerative program leading to functional recovery, underscoring the potential of a reprogramming approach to sensory regeneration. : The mature mouse utricle, which detects linear acceleration, displays limited regeneration, but whether function returns is unknown. Sayyid et al. show that regenerated hair cells appear and mature over months, resulting in a limited, unsustained functional recovery. Atoh1 overexpression enhances regeneration and leads to a sustained recovery of vestibular function. Keywords: utricle, hair cell, vestibular, sensory, regeneration, proliferation, Atoh1, vestibular evoked potential |
| first_indexed | 2024-12-21T14:43:08Z |
| format | Article |
| id | doaj.art-50e335d5d2594b9982ece8668b087d61 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T14:43:08Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-50e335d5d2594b9982ece8668b087d612022-12-21T19:00:06ZengElsevierCell Reports2211-12472019-07-01282312324.e4Atoh1 Directs Regeneration and Functional Recovery of the Mature Mouse Vestibular SystemZahra N. Sayyid0Tian Wang1Leon Chen2Sherri M. Jones3Alan G. Cheng4Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Special Education and Communication Disorders, College of Education and Human Sciences, University of Nebraska, Lincoln, NE 68583, USADepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Corresponding authorSummary: Utricular hair cells (HCs) are mechanoreceptors required for vestibular function. After damage, regeneration of mammalian utricular HCs is limited and regenerated HCs appear immature. Thus, loss of vestibular function is presumed irreversible. Here, we found partial HC replacement and functional recovery in the mature mouse utricle, both enhanced by overexpressing the transcription factor Atoh1. Following damage, long-term fate mapping revealed that support cells non-mitotically and modestly regenerated HCs displaying no or immature bundles. By contrast, Atoh1 overexpression stimulated proliferation and widespread regeneration of HCs exhibiting elongated bundles, patent mechanotransduction channels, and synaptic connections. Finally, although damage without Atoh1 overexpression failed to initiate or sustain a spontaneous functional recovery, Atoh1 overexpression significantly enhanced both the degree and percentage of animals exhibiting sustained functional recovery. Therefore, the mature, damaged utricle has an Atoh1-responsive regenerative program leading to functional recovery, underscoring the potential of a reprogramming approach to sensory regeneration. : The mature mouse utricle, which detects linear acceleration, displays limited regeneration, but whether function returns is unknown. Sayyid et al. show that regenerated hair cells appear and mature over months, resulting in a limited, unsustained functional recovery. Atoh1 overexpression enhances regeneration and leads to a sustained recovery of vestibular function. Keywords: utricle, hair cell, vestibular, sensory, regeneration, proliferation, Atoh1, vestibular evoked potentialhttp://www.sciencedirect.com/science/article/pii/S2211124719307946 |
| spellingShingle | Zahra N. Sayyid Tian Wang Leon Chen Sherri M. Jones Alan G. Cheng Atoh1 Directs Regeneration and Functional Recovery of the Mature Mouse Vestibular System Cell Reports |
| title | Atoh1 Directs Regeneration and Functional Recovery of the Mature Mouse Vestibular System |
| title_full | Atoh1 Directs Regeneration and Functional Recovery of the Mature Mouse Vestibular System |
| title_fullStr | Atoh1 Directs Regeneration and Functional Recovery of the Mature Mouse Vestibular System |
| title_full_unstemmed | Atoh1 Directs Regeneration and Functional Recovery of the Mature Mouse Vestibular System |
| title_short | Atoh1 Directs Regeneration and Functional Recovery of the Mature Mouse Vestibular System |
| title_sort | atoh1 directs regeneration and functional recovery of the mature mouse vestibular system |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719307946 |
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