Vestibular and Auditory Hair Cell Regeneration Following Targeted Ablation of Hair Cells With Diphtheria Toxin in Zebrafish

Jimenez, Erin and Slevin, Claire C. and Colón-Cruz, Luis and Burgess, Shawn M. (2021) Vestibular and Auditory Hair Cell Regeneration Following Targeted Ablation of Hair Cells With Diphtheria Toxin in Zebrafish. Frontiers in Cellular Neuroscience, 15. ISSN 1662-5102

[thumbnail of pubmed-zip/versions/1/package-entries/fncel-15-721950/fncel-15-721950.pdf] Text
pubmed-zip/versions/1/package-entries/fncel-15-721950/fncel-15-721950.pdf - Published Version

Download (4MB)

Abstract

Millions of Americans experience hearing or balance disorders due to loss of hair cells in the inner ear. The hair cells are mechanosensory receptors used in the auditory and vestibular organs of all vertebrates as well as the lateral line systems of aquatic vertebrates. In zebrafish and other non-mammalian vertebrates, hair cells turnover during homeostasis and regenerate completely after being destroyed or damaged by acoustic or chemical exposure. However, in mammals, destroying or damaging hair cells results in permanent impairments to hearing or balance. We sought an improved method for studying hair cell damage and regeneration in adult aquatic vertebrates by generating a transgenic zebrafish with the capacity for targeted and inducible hair cell ablation in vivo. This model expresses the human diphtheria toxin receptor (hDTR) gene under the control of the myo6b promoter, resulting in hDTR expressed only in hair cells. Cell ablation is achieved by an intraperitoneal injection of diphtheria toxin (DT) in adult zebrafish or DT dissolved in the water for larvae. In the lateral line of 5 days post fertilization (dpf) zebrafish, ablation of hair cells by DT treatment occurred within 2 days in a dose-dependent manner. Similarly, in adult utricles and saccules, a single intraperitoneal injection of 0.05 ng DT caused complete loss of hair cells in the utricle and saccule by 5 days post-injection. Full hair cell regeneration was observed for the lateral line and the inner ear tissues. This study introduces a new method for efficient conditional hair cell ablation in adult zebrafish inner ear sensory epithelia (utricles and saccules) and demonstrates that zebrafish hair cells will regenerate in vivo after this treatment.

Item Type: Article
Subjects: OA Open Library > Medical Science
Depositing User: Unnamed user with email support@oaopenlibrary.com
Date Deposited: 13 Apr 2023 06:49
Last Modified: 02 Mar 2024 04:19
URI: http://archive.sdpublishers.com/id/eprint/499

Actions (login required)

View Item
View Item