Fish n' chicks: Model recipes for hair-cell regeneration?

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In nearly every waking moment, our brains respond to signals that originate from hair cells. These cells reside in six separate epithelia in our internal ears and are detectors of head rotation, gravity, and sound. Hair cells can be killed by loud sounds, certain antibiotics, and other drugs. Some are lost through infections and aging. Any loss is potentially significant, since hair cells are not added to the human ear after birth, according to the accepted view. ” Nerve deafness,” a permanent form of hearing loss, actually results from loss of hair cells in most cases, not from damage to nerves. Permanent balance dysfunctions also result from hair-cell loss in many cases. These conditions affect 10% of the population and 25% of people over the age of 65, making hair-cell loss one of the most common neurological deficits. Unfortunately, despite considerable progress in understanding the physiology of hair cells and the neural basis of hearing and balance, most deficits that result from hair-cell loss have remained irreversible. In contrast to the situation in humans, hair cells are produced throughout life in the ears of fish, amphibians, and birds. The discovery that hundreds of thousands of hair cells are added to the ears of postembryonic sharks led to the proposal that hair-cell loss might be repaired via regenerative replacement mechanisms that could form the basis for regenerative treatments. Hair cell regeneration does indeed occur in the ears of many vertebrates, even in organs such as the chick's cochlea, where cell production normally ends before birth. Treatments that cause permanent hearing and balance deficits in humans also kill hair cells in birds, fish, and amphibians, but in those species the loss of hair cells can evoke cell proliferation at the site of damage. The newly generated cells differentiate into supporting cells and replacement hair cells, which make synapses with surviving neurons. In nonmammalian ears, these repair processes can lead to rapid recovery from hearing and balance deficits that would be permanent in a human (references in[ 3 and 5 ]). Supporting Cells Are Relatively Undifferentiated in the Most Plastic Hair-Cell Epithelia Prototypical hair-cell epithelia contain only two resident cell types: hair cells and the supporting cells that cover the basal lamina and extend to the apical surface between neighboring hair cells. Terminal neurites of afferent and efferent neurons and small numbers of roving leukocytes are also present. Proliferative, multipotential progenitor cells appear to be required for the initiation of regeneration in amphibian limbs and for most forms of regeneration in animals (references in[ 1 ]). Consistent with that, supporting cells in fish, amphibians, and birds proliferate rapidly after hair cells have been lost, and those epithelia regenerate lost hair cells. In balance epithelia from rodent and human ears, small numbers of supporting cells will proliferate in culture after hair cells have been killed, but the response is much weaker than in nonmammals. All those epithelia contain relatively undifferentiated supporting cells that cannot be reliably subdivided on the basis of histological characteristics, so a relative lack of supporting cell differentiation and a capacity for regenerative proliferation may be linked ( Table 1 ). Such a linkage is consistent with the apparent lack of plasticity in the organ of Corti, the auditory epithelium of placental mammals. Its supporting cells are structurally specialized as five differentiated subtypes, which are all effectively nonproliferative during postembryonic life. In rare cases of damage in cultures from neonates, the organ of Corti may be able to replace hair cells after birth, and that also can occur through a cell-fate change in embryonic organs (Kelley et al., 1996). One study of organs of Corti cultured from neonatal rats has reported dramatic and complete healing after hair-cell poisoning by an antibiotic, but other investigators have challenged that report. Partial healing responses in this organ have recently been reported.




Corwin, J. T., & Oberholtzer, J. C. (1997). Fish n’ chicks: Model recipes for hair-cell regeneration? Neuron. Cell Press.

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