Regeneration in avian hair cell epithelia: identification of intracellularsignals required for S-phase entry

Balance epithelia in birds closely resemble their mammalian counterparts, b ut their cells turnover rapidly and they quickly regenerate hair cells, lea ding to functional recovery from damage that would be permanent for a mamma l. We isolated and cultured sheets of the chicken's utricular epithelium in bromo-deoxyuridine and specific inhibitors of different intracellular sign alling pathways to identify signals that influence turnover and regeneratio n. Synthesis (S-phase) entry was effectively blocked by inhibition of PI3-K , TOR or MAPK, and significantly decreased by inhibitors of PKC. Comparison s indicate that activated PI3-K and TOR are required for S-phase entry in b oth avian and mammalian balance epithelia, but activation of the MAPK pathw ay appears to have a more significant role in avian utricles than in mammal s. The dissimilarities in the requirements for these signalling pathways do not appear sufficient to explain the marked difference in regenerative cap acity between the ears of birds and mammals.