Retinoic acid-mediated increase in TrkA expression is sufficient to elicit NGF-dependent survival of sympathetic neurons.
Sympathetic neurons depend on the classical neurotrophin NGF for survival by the time they innervate their targets, but the mechanisms controlling the onset of NGF responsiveness in developing neuroblasts have not been defined. Immature chick sympathetic neurons are unresponsive to NGF, but express low mRNA levels of the high-affinity NGF receptor trkA. Treatment with retinoic acid (RA) leads to increased levels of both trkA mRNA and protein, a response mediated through retinoic acid receptor alpha (RAR alpha). Ectopic expression of trkA in these cells results in the ability to survive with NGF, suggesting that RA-induced trkA expression is sufficient to elicit NGF-dependent survival. Our data establish a mechanism controlling NGF responsiveness and implicate a function for RA at defined late stages of neuron development.
D000818:Animals; D001667:Binding, Competitive; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D015870:Gene Expression / Q000235:genetics*; D009414:Nerve Growth Factors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D013564:Sympathetic Nervous System / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology*
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D014212:Tretinoin; D011505:Protein-Tyrosine Kinases