Hair Cell Regeneration: The Identities of Progenitor Cells, Potential Triggers and Instructive Cues

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Abstract
Hair cells are produced and accumulate in the ears of fish and amphibians as they grow during postembryonic life; hair cell regeneration occurs in lateral line organs in those groups and in the cochlea in birds. Continuous time-lapse microscopy has directly demonstrated that supporting cells divide to give rise to hair cells during regeneration in lateral line neuromasts. Supporting cells also appear to give rise to hair cells during regeneration in the avian ear, but additional cell types have been proposed as hair cell progenitors. Alternative interpretations of current evidence are discussed in relation to the possibility that supporting cells may be the common progenitor in all cases of hair cell regeneration. The regenerative proliferation of hair cells in birds occurs in populations of cells that are mitotically quiescent in undamaged ears. Evidence suggests that the extrusion of damaged hair cells and the breaking of intercellular junctional adhesions may be a trigger for regenerative proliferation. The potential triggering influence of phagocytes is also discussed. The differentiation of replacement cells during regeneration in the cochlea may be regulated by surface interactions between cells. A model that could account for the reconstitution of the mosaic pattern of hair cells and supporting cells is proposed.