Ongoing Death and Replacement of Sensory Receptors in the Mature Inner Ear

Sensory hair cells in the mammalian inner ear are produced during a limited period of embryonic development. Some of these cells are lost during adult life as a consequence of normal aging, but many hair cells appear to be capable of surviving for an animal's entire lifetime (which can exceed 80 years in some species). In contrast, hair cells in the vestibular organs of birds have a relatively short life span of 2 to 3 months. We are interested in understanding the biological basis for the very different patterns of hair cell survival that are observed in mammals and birds. Our data suggest that hair cells in the mature avian ear undergo a spontaneous form of programmed cell death (apoptosis) and are then quickly replaced by new hair cells that arise from the division of epithelial supporting cells. Additional experiments have shown that both spontaneous and aminoglycoside-induced hair cell death can be prevented by inhibition of certain signaling molecules in the apoptotic pathway. Such treatment also leads to a corresponding reduction in supporting cell proliferation, suggesting that proliferation in these organs is triggered by hair cell death. Other studies in our lab are aimed at identifying signals that regulate the production of replacement hair cells. We have shown that the signaling molecules N-cadherin, β-catenin, and focal adhesion kinase are present in the utricular sensory epithelium and that high levels of phosphotyrosine immunoreactivity are present at cell-cell junctions and focal contacts of proliferating cells. Experiments have demonstrated that the proliferation of cultured supporting cells is influenced by the cell adhesion molecule N-cadherin and by the composition of the extracellular matrix. These results suggest that cell-cell contact and cell-substrate interactions may be critical influences on the regulation of sensory regeneration in the inner ear.