Regeneration in avian hair cell epithelia: identification of intracellular signals required for S-phase entry.
Balance epithelia in birds closely resemble their mammalian counterparts, but their cells turnover rapidly and they quickly regenerate hair cells, leading to functional recovery from damage that would be permanent for a mammal. We isolated and cultured sheets of the chicken's utricular epithelium in bromo-deoxyuridine and specific inhibitors of different intracellular signalling pathways to identify signals that influence turnover and regeneration. Synthesis (S-phase) entry was effectively blocked by inhibition of PI3-K, TOR or MAPK, and significantly decreased by inhibitors of PKC. Comparisons indicate that activated PI3-K and TOR are required for S-phase entry in both avian and mammalian balance epithelia, but activation of the MAPK pathway appears to have a more significant role in avian utricles than in mammals. The dissimilarities in the requirements for these signalling pathways do not appear sufficient to explain the marked difference in regenerative capacity between the ears of birds and mammals.
Witte
M C
MC
Department of Otolaryngology, School of Medicine, University of Virginia, HSC Box 396, Cobb Hall, Charlottesville, VA 22908, USA.
Montcouquiol
M
M
Corwin
J T
JT
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D047310:Apigenin; D001798:Blood Proteins / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002645:Chickens; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016196:S Phase / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D047310:Apigenin; D001798:Blood Proteins; D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D009281:Naphthalenes; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D000077191:Wortmannin; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C058819:calphostin C; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one