Regeneration and functional recovery of the adult mouse utricle
Abstract/Contents
- Abstract
- Utricular hair cells (HC) are mechanoreceptors required for vestibular function. After damage, the mammalian utricle only marginally regenerates; thus, loss of vestibular function is presumed irreversible. Whether mammalian HC regeneration restores function is unclear. Here, we found partial HC replacement and functional recovery in the spontaneously regenerating mature mouse utricle, both enhanced by overexpressing the transcription factor Atoh1. Following toxin-induced HC death and vestibular dysfunction, long-term fate-mapping revealed that extrastriolar supporting cells non-mitotically and modestly regenerated HCs displaying nascent bundles. In the damaged but not undamaged utricle, constitutive Atoh1 overexpression stimulated proliferation and widespread regeneration of HCs (~80%) exhibiting elongated bundles, patent mechanotransduction channels, and synaptic connections. Finally, significantly more animals recovered vestibular function with Atoh1 overexpression than with damage only. Therefore, the mature, damaged utricle harbors a previously unrecognized Atoh1-responsive regenerative potential leading to functional recovery, underscoring the promise of a reprogramming approach to sensory regeneration.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Sayyid, Zahra N |
|---|---|
| Degree supervisor | Cheng, Alan (Alan G.) |
| Degree committee member | Heller, Stefan |
| Degree committee member | Nusse, Roel, 1950- |
| Degree committee member | Raymond, Jennifer L |
| Thesis advisor | Heller, Stefan |
| Thesis advisor | Nusse, Roel, 1950- |
| Thesis advisor | Raymond, Jennifer L |
| Associated with | Stanford University, Neurosciences Program. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Zahra N. Sayyid. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Zahra Nabi Sayyid
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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