Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Evaluating the Death and Recovery of Lateral Line Hair Cells Following Repeated Neomycin Treatments

Version 1 : Received: 3 October 2021 / Approved: 4 October 2021 / Online: 4 October 2021 (10:27:34 CEST)

A peer-reviewed article of this Preprint also exists.

Journal reference: Life 2021
DOI: 10.3390/life11111180

Abstract

Acute chemical ablation of lateral line hair cells is an important tool to understand lateral line-mediated behaviors in free-swimming fish larvae and adults. However, lateral line-mediated behaviors have not been described in fish larvae prior to swim bladder inflation, possibly because single doses of ototoxin do not effectively silence lateral line function at early developmental stages. To determine if ototoxins can effectively silence the lateral line during early development, we repeatedly expose zebrafish larvae to the ototoxin neomycin during a 36-hour period from 3-4 days post-fertilization (dpf). We use simultaneous transgenic and vital dye labeling of hair cells to compare 6- hour and 12-hour repeated treatment timelines and neomycin concentrations between 0–400 µM in terms of larval survival, hair cell death, regeneration, and functional recovery. Following exposure to neomycin, we find that the emergence of newly functional hair cells outpaces cellular regeneration, likely due to the maturation of ototoxin-resistant hair cells that survive treatment. Furthermore, hair cells of 4 dpf larvae exhibit faster recovery compared to 3 dpf larvae. Our data suggest that the rapid functional maturation of ototoxin-resistant hair cells limits the effectiveness of chemical-based methods to disrupt lateral line function. Furthermore, we show that repeated neomycin treatments can continually ablate lateral line hair cells between 3–4 dpf in larval zebrafish.

Keywords

zebrafish; lateral line; neuromast; hair cell; ototoxicity; toxicity; regeneration; cell death; neomycin; aminoglycosides

Subject

LIFE SCIENCES, Cell & Developmental Biology

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