New hair cells arise from supporting cell conversion in the acoustically damaged chick inner ear

Supporting cell mitosis contributes significantly to hair cell regeneration in the acoustically damaged bird inner ear. Yet there may be another mechanism of hair cell replacement: supporting cell conversion. This study used cytosine arabinoside (Ara-C), an inhibitor of DNA synthesis, to better determine whether supporting cells could transdifferentiate into hair cells without cell division. Chicks received Ara-C injections after acoustic overstimulation. Scanning microscopic studies of the basilar papillae revealed several unpaired, immature hair cells. To ensure Ara-C's blockage of DNA synthesis, one group of birds received both Ara-C and bromodeoxyuridine (BrdU), while another group had BrdU only. Immunocytochemical analysis of Ara-C/BrdU and BrdU papillae indicated zero and 16 dividing cells, respectively. This difference confirmed that Ara-C blocked DNA synthesis, arresting supporting cell mitosis. These data strongly suggest that supporting cells can convert into hair cells.