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

Eur J Neurosci. 2001 Sep;14(5):829-38. doi: 10.1046/j.0953-816x.2001.01695.x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apigenin
  • Blood Proteins / pharmacology
  • Butadienes / pharmacology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Chickens
  • Chromones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Hair Cells, Auditory / cytology*
  • Hair Cells, Auditory / enzymology*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Nitriles / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Regeneration / physiology*
  • Ribosomal Protein S6 Kinases / antagonists & inhibitors
  • Ribosomal Protein S6 Kinases / metabolism
  • S Phase / drug effects
  • S Phase / physiology*
  • Sirolimus / pharmacology
  • Wortmannin

Substances

  • Androstadienes
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Blood Proteins
  • Butadienes
  • Chromones
  • Enzyme Inhibitors
  • Flavonoids
  • Morpholines
  • Naphthalenes
  • Nitriles
  • Phosphoinositide-3 Kinase Inhibitors
  • U 0126
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Apigenin
  • Ribosomal Protein S6 Kinases
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • calphostin C
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Sirolimus
  • Wortmannin