Target-derived cardiotrophin-1 and insulin-like growth factor-I promote neurite growth and survival of developing oculomotor neurons.
Several trophic factors support the survival of developing motoneurons, but it is not known whether these factors act in a retrograde fashion from the motoneuron target muscle or are derived from other sources. Cardiotrophin-1 (CT-1) and the insulin-like growth factors (IGFs) are candidate target-derived motoneuron survival factors as both are expressed in muscle during naturally occurring motoneuron death and, applied systemically, support the survival of developing motoneurons. By using the embryonic chick oculomotor system, we show that CT-1 and IGF-I promote neurite outgrowth from E13-derived oculomotor explants and are retrogradely transported from muscle to nerve cell body in vivo, and injection of CT-1 or IGF-I into eye muscles increases motoneuron survival by 20 and 30%, respectively, as evidenced by calibrated stereological counting techniques. Pharmacological depletion of endogenous target-derived IGF-I in vivo reduces oculomotor neuron survival by up to 30% in a dose-dependent manner. These results significantly extend previous studies using systemic administration of trophic factors and are the first to demonstrate a target-derived retrograde mechanism of developing motoneuron survival factors.
Rind
Howard B
HB
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
von Bartheld
Christopher S
CS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D003574:Cytochrome c Group / Q000493:pharmacokinetics / Q000502:physiology; D016207:Cytokines / Q000493:pharmacokinetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000493:pharmacokinetics / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000493:pharmacokinetics / Q000502:physiology; D007457:Iodine Radioisotopes; D009046:Motor Neurons / Q000502:physiology* / Q000648:ultrastructure; D016501:Neurites / Q000502:physiology*; D009801:Oculomotor Muscles / Q000294:innervation; D009802:Oculomotor Nerve / Q000166:cytology* / Q000196:embryology
D003574:Cytochrome c Group; D016207:Cytokines; D018974:Insulin-Like Growth Factor Binding Protein 4; D007457:Iodine Radioisotopes; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C092073:cardiotrophin 1