Development of an Optogenetic Tool for Targeted Sensory Hair Cell Ablation in Zebrafish

Abstract

Mechanosensory hair cells convert mechanical information into neuronal signals. Mutations in the genes required for hair cell function cause deafness and lead to the degeneration of sensory hair cells. Mammals are unable to regenerate these cells, leading to the permanent loss of hair cells. Research efforts are being made to stimulate hair cell regeneration in mammals and to repair genetic mutations via gene therapy to restore hearing. However, if sensory-deficient hair cells are unable to be regenerated, the effectiveness of gene therapy will be limited. To date, there are no studies examining whether mutant hair cells are able to regenerate after cell death. Other vertebrates, such as amphibians, birds, reptiles and fish, possess the ability to regenerate mechanosensory hair cells after cell death. Thus, it is of great value to investigate the genetic factors affecting the regeneration of the sensory hair cells in these species as a step towards initiating this ability in humans. This experiment uses the zebrafish model system to investigate the ability of sensory- deficient hair cells to resist ototoxic insults, and the proliferative and regenerative properties of the lateral line organ. To look at the regeneration capabilities of MET mutants, ablation methods were used to target sensory hair cells using the OptoBax system in zebrafish.