The Cell Cycle and the Development and Regeneration of Hair Cells

Abstract

Abstract The replication of cells occurs by a process known as the cell cycle, which is under multiple forms of regulation. Cell proliferation is an integral part of the development of the inner ear. Generation of the otic sensory epithelia involves coordinated periods of cell division. However, commitment of cells in the developing sensory epithelia to a hair cell fate and the differentiation of hair cells from committed precursors are postmitotic processes, which occur after the establishment of a zone of nonproliferating cells within the epithelium. The suppression of cell division by regulators of the cell cycle is both temporally and functionally linked to hair cell development. Animals lacking cell cycle regulatory proteins can exhibit supernumerary hair cells and exhibit hearing loss. The absence of hair cell regeneration in mammals appears to be related to both mitotic and postmitotic factors. Unlike in fish and birds, cell proliferation is rare in mammalian sensory epithelia following hair cell damage. Cell division can be dramatically increased in mammalian vestibular sensory epithelia by a variety of factors. However, the resulting cells rarely adopt a hair cell fate. As with the cell cycle, our increased understanding of the factors that determine hair cell fate selection may allow us to overcome barriers to hair cell regeneration in mammals.