Adult Zebrafish Lateral Line: A Well Supported System

Abstract

Hair cells are required for hearing and balance. Hair cell death is caused by multiple environmental insults, such as prolong exposure to loud noises, aminoglycoside antibiotics, some chemotherapeutics, and heavy metals, and hair cell loss is irreversible in humans. However, many other vertebrates such as, birds, fish and amphibians have the ability to replaced lost hair cells. Zebrafish has quickly become an excellent modeled to study hair cell biology. Aside from the hair cells found in the inner ear, zebrafish have externally located hair cells on the head and body that allow them to detect changes in water currents. Also, larval zebrafish can quickly regenerate lost hair cells after traumatic damage. How hair cell precursors are replenished or maintained throughout the animal’s life is still unknown. I investigated lateral line hair cell and support cell maintenance in adult zebrafish, in which growth is largely complete. I demonstrate that adult zebrafish not only replenish hair cells after a single instance of hair cell damage, but also maintain hair cells and support cells after multiple rounds of damage and regeneration. I observed that hair cells undergo continuous turnover in adult zebrafish in the absence of damage. Mitotically-distinct support cell populations were identified and show that hair cells regenerate from underlying support cells in a region-specific manner. Using the transgenic Zebrabow-M fish line, I performed long-term multicolor clonal analysis to discover that lateral line neuromast drift towards clonality. However, I also observe that some neuromasts reach equilibrium and may indicate that multiple progenitors act to maintain the lateral line neuromast. Our results demonstrate that there are distinct support cell populations in the lateral line, which may help explain why zebrafish hair cell regeneration is extremely robust, retained throughout life, and potentially unlimited in regenerative capacity.