Hair cells of the inner ear are damaged by intense noise, aging, and 
aminoglycoside antibiotics. Gentamicin causes oxidative damage to hair cells, 
inducing apoptosis. In mammals, hair cell loss results in a permanent deficit in 
hearing and balance. In contrast, avians can regenerate lost hair cells to 
restore auditory and vestibular function. This study examined the changes of 
myosin VI and myosin VIIa, two unconventional myosins that are critical for 
normal hair cell formation and function, during hair cell death and 
regeneration. During the late stages of apoptosis, damaged hair cells are 
ejected from the sensory epithelium. There was a 4-5-fold increase in the 
labeling intensity of both myosins and a redistribution of myosin VI into the 
stereocilia bundle, concurrent with ejection. Two separate mechanisms were 
observed during hair cell regeneration. Proliferating supporting cells began DNA 
synthesis 60 hours after gentamicin treatment and peaked at 72 hours 
postgentamicin treatment. Some of these mitotically produced cells began to 
differentiate into hair cells at 108 hours after gentamicin (36 hours after 
bromodeoxyuridine (BrdU) administration), as demonstrated by the colabeling of 
myosin VI and BrdU. Myosin VIIa was not expressed in the new hair cells until 
120 hours after gentamicin. Moreover, a population of supporting cells expressed 
myosin VI at 78 hours after gentamicin treatment and myosin VIIa at 90 hours. 
These cells did not label for BrdU and differentiated far too early to be of 
mitotic origin, suggesting they arose by direct transdifferentiation of 
supporting cells into hair cells.