Hair cells of the inner transduce mechanical stimui to electrical signals transmitted to the brain. Hair cells of the auditory organs respond to sound stimuli for hearing perception; those in the vestibular organs respond to gravity and head movements for perception of balance. Hair cells are so named because they have actin-rich protrusions, stereocilia, at their apical end. Displacement of stereocilia opens ion channels resulting in depolarization and release of transmitter from synapses at the basal end of the cell to terminals of innervating afferent nerves. Damage and loss of hair cells are leading causes of hearing and balance disorders, which affect over 40 million people in the US. Hair cells are susceptible to environmental insults, including noise, chemical exposure and accumulated damage during aging. Genetic disorders are common, affecting more than 1:500 children. Hair cell loss in humans is irreversible.
We use the zebrafish lateral line system to study hair cells. Like those of the inner ear, lateral line hair cells respond to fluid movement and synapse with afferent neurons. However as they are located on the body surface they are readily accessible for visualization and manipulation. In contrast to humans, zebrafish regenerate their hair cells from a dedicated pool of precursors. We use genetic manipulation such as CRISPR and in vivo imaging using encoded fluorescent reporters to study hair cell development, death and regeneration. Our studies are leading to therapeutic approaches to prevent hair cell damage and potentially restore function.