Recent reports documented the ability of the posthatch avian vestibular epithelia to produce hair cells continually at a low rate. This project was designed to investigate whether, in addition, the chicken vestibular system is capable of regenerating its sensory epithelium in response to a lesion. Aminoglycoside injections were given to young birds in order to damage the vestibular epithelium. Tritiated thymidine injections were used to label cells produced in response to the lesion. Treatment and age-matched control animals were killed at 1 day, 20 days, or 60 days after aminoglycoside injections, and vestibular organs were processed for autoradiography. Our results show that the chicken vestibular sensory epithelium is capable of regenerating hair cells after severe damage. Moreover, the epithelium is capable of complete anatomical recovery. Finally, drug damage increases the pace at which hair cells are replaced, compared to the rate of hair cell turnover in untreated tissue.

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Postembryonic production of sensory hair cells occurs in both normal and aminoglycoside-damaged avian inner ears. The cellular source and mechanism that results in new differentiated hair cells were investigated in the avian vestibular epithelia using three distinct cell-cycle-specific labeling methods to identify proliferating sensory epithelial cells. First, immunocytochemical detection of the proliferating cell nuclear antigen, an auxiliary protein of DNA polymerase, allowed labeling of cells in late G1, S, and early G2 phases of the cell cycle. Second, a pulse-fix tritiated thymidine autoradiographic protocol was used to identify cells in S phase of the cell cycle. Finally, Hoechst 33342, a fluorescent DNA stain, was used to identify epithelial cells in mitosis. The distribution of cells active in the cell cycle within the normal and ototoxin-damaged vestibular epithelium suggests that supporting cells within the sensory epithelia are the cellular precursors to the regenerated hair cells. Differences between the proliferation marker densities in control and damaged end organs indicate that the upregulation of mitotic activity observed after streptomycin treatment is due primarily to an increase in the number of dividing progenitor cells. The differences between the extent of ototoxic damage and the level of reparative proliferative response suggest a generalized stimulus, such as a soluble chemical factor, plays a role in initiating regeneration. Finally, after DNA replication is initiated, progenitor cell nuclei migrate from their original location close to the basement membrane to the lumenal surface, where cell division occurs. This pattern of intermitotic nuclear migration is analogous to that observed in the developing inner ear and neural epithelium.

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