Fish n' Chicks: Model Recipes for Hair-Cell Regeneration?

after hair cells have been killed, but the response is In nearly every waking moment, our brains respond to much weaker than in nonmammals. All those epithelia signals that originate from hair cells. These cells reside contain relatively undifferentiated supporting cells that in six separate epithelia in our internal ears and are cannot be reliably subdivided on thebasis of histological detectors of head rotation, gravity, and sound. Hair cells characteristics, so a relative lack of supporting cell difcan be killed by loud sounds, certain antibiotics, and ferentiation and a capacity for regenerative proliferation other drugs. Some are lost through infections and aging. may be linked (Table 1). Such a linkage is consistent Any loss is potentially significant, since hair cells are with the apparent lack of plasticity in the organ of Corti, not added to the human ear after birth, according to the the auditory epithelium of placental mammals. Its supaccepted view. “Nerve deafness,” a permanent form of porting cells are structurally specialized as five differenhearing loss, actually results from loss of hair cells in tiated subtypes, which are all effectively nonproliferative most cases, not from damage to nerves. Permanent during postembryonic life. In rare cases of damage in balance dysfunctions also result from hair-cell loss in cultures from neonates, the organ of Corti may be able many cases. These conditions affect z10% of the poputo replace hair cells after birth, and that also can occur lation and 25% of people over the age of 65, making hairthrough a cell-fate change in embryonic organs (Kelley cell loss one of the most common neurological deficits. et al., 1996). One study of organs of Corti cultured from Unfortunately, despite considerable progress in underneonatal rats has reported dramatic and complete healstanding the physiology of hair cellsand the neural basis ing after hair-cell poisoning by an antibiotic, but other of hearing and balance, most deficits that result from investigators have challenged that report. Partial healing hair-cell loss have remained irreversible. responses in this organ have recently been reported. In contrast to the situation in humans, hair cells are Hair-Cell Regeneration in Chicks produced throughout life in the ears of fish, amphibians, Each chick cochlea contains roughly 10,000 hair cells and birds. The discovery that hundreds of thousands of that form a phenotypic gradient, wherein the cells differ hair cells are added to the ears of postembryonic sharks progressively in size and shape along and across the led to the proposal that hair-cell loss might be repaired epithelium, as do the numbers, dimensions, and geovia regenerative replacement mechanisms that could metric arrangements of the stereocilia in their hair bunform the basis for regenerative treatments. Hair cell redles. There is little, if any, proliferation in the undamaged generation does indeed occur in the ears of many verteauditory epithelia, but a loss of hair cells evokes proliferbrates, even in organs such as the chick’s cochlea, ation within z200 mm of the site of loss, beginning after where cell production normally ends before birth. Treat16 hr (Warchol and Corwin, 1996). It appears that the ments that cause permanent hearing and balance defidivision of a supporting cell can give rise to one cell cits in humans also kill hair cells in birds, fish, and amthat becomes a hair cell and to another that becomes phibians, but in those species the loss of hair cells can a supporting cell (Jones and Corwin, 1996). Supporting evoke cell proliferation at the site of damage. The newly cell divisions may also give rise to pairs of supporting generated cells differentiate into supporting cells and cells and pairs of hair cells. One hypothesis proposes replacement hair cells, which make synapses with surthat new cells become hair cells by default unless they viving neurons. In nonmammalian ears, these repair prodevelop in contact with a cell already determined as a cesses can lead to rapid recovery from hearing and hair cell. Homologs of the Delta-Notch signaling system balance deficits that would be permanent in a human of Drosophila may control cell-fate choices in hair cell (references in Corwin and Warchol, 1991; Cotanche and epithelia via lateral inhibition during development (Whit-