Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice

Abstract

Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals. We used fate-mapping and other methods to demonstrate that utricular type II vestibular hair cells undergo turnover in adult mice under normal conditions. We found that supporting cells phagocytose both type I and II hair cells. Plp1-CreERT2-expressing supporting cells replace type II hair cells. Type I hair cells are not restored by Plp1-CreERT2-expressing supporting cells or by Atoh1-CreERTM-expressing type II hair cells. Destruction of hair cells causes supporting cells to generate 6 times as many type II hair cells compared to normal conditions. These findings expand our understanding of sensorineural plasticity in adult vestibular organs and further elucidate the roles that supporting cells serve during homeostasis and after injury.Cells in the inner ear called hair cells sense sound waves and head movements, allowing us to hear and maintain balance. In non-mammals such as birds and fish, the hair cells responsible for balance die and are replaced (in a process known as turnover) throughout life. However, it is largely assumed that no new balance hair cells are made in adult mammals such as humans and mice. This would mean that injured hair cells are never replaced, which could cause balance problems such as dizziness over time.There have been hints in past studies that perhaps some balance hair cells die or are newly made in adult mammals. Using a variety of new cell labeling and tracking methods in different types of mutant mice, Bucks et al. now show that the turnover of balance hair cells happens in adult mice under normal conditions. Both types of balance hair cells – known as type I and type II – are removed by supporting cells that surround the hair cells. In addition, the supporting cells can convert into new type II hair cells, but not type I hair cells, and type II hair cells do not convert into new type I hair cells.To compare these results with what happens after hair cell damage, Bucks et al. injected a toxin into mutant mice to kill most hair cells. This revealed that supporting cells make 6 times as many hair cells after severe damage than under normal conditions, but still only make type II hair cells.One important issue to study next is whether type I hair cells are ever created in adulthood. Many elderly people develop balance problems that lead to catastrophic falls. Perhaps one reason this occurs is because type I hair cells cannot be replaced in humans.