Feathers and fins: non-mammalian models for hair cell regeneration

Abstract

Death of mechanosensory cells in the inner ear results in two profound disabilities: hearing loss and balance disorders. Although mammals lack the capacity to regenerate hair cells, recent studies in mice and other rodents have offered valuable insight into strategies for stimulating hair cell regeneration in mammals. Investigations of model organisms that retain the ability to form new hair cells after embryogenesis, such as fish and birds, are equally important and have provided clues as to the cellular and molecular mechanisms that may block hair cell regeneration in mammals. Here, we summarize studies on hair cell regeneration in the chicken and the zebrafish, discuss specific advantages of each model, and propose future directions for the use of non-mammalian models in understanding hair cell regeneration.

Fig. 1

Methods of Hair Cell Replacement. The production of hair cells (depicted here as fish hair cells, which retain kinocillia) may occur by several methods. (A) Supporting Cells (SC) may rapidly produce hair cells by direct transdifferentiation; direct, phenotypic conversion to a hair cell (HC) without the requirement for mitosis. When HC replacement depends on mitosis there are several possible mechanisms. (B) Symmetric division of one SC produces two HCs, rapidly replacing HC but eventually leading to a depletion of SC. (C) Asymmetric SC division produces one HC and one SC, replacing lost HC more slowly but replenishing the SC pool. (D) Symmetric SC division may produce two SC as a method of maintaining the SC population. This symmetric division could occur in tandem with, or following symmetric SC divisions resulting in two hair cells. One final alternative, not depicted, is that SCs produce HC precursors distinct from a fully differentiated HC and thus introduce a middle stage to all of the methods depicted above.