PMID- 10842241 OWN - NLM STAT- MEDLINE DCOM- 20000724 LR - 20191104 IS - 0022-3034 (Print) IS - 0022-3034 (Linking) VI - 43 IP - 3 DP - 2000 Jun 5 TI - Differential effects of the trophic factors BDNF, NT-4, GDNF, and IGF-I on the isthmo-optic nucleus in chick embryos. PG - 289-303 AB - The isthmo-optic nucleus (ION) of chick embryos is a model system for the study of retrograde trophic signaling in developing CNS neurons. The role of brain-derived neurotrophic factor (BDNF) is well established in this system. Recent work has implicated neurotrophin-4 (NT-4), glial cell line-derived neurotrophic factor (GDNF), and insulin-like growth factor I (IGF-I) as additional trophic factors for ION neurons. Here it was examined in vitro and in vivo whether these factors are target-derived trophic factors for the ION in 13- to 16-day-old chick embryos. Unlike BDNF, neither GDNF, NT-4, nor IGF-I increased the survival of ION neurons in dissociated cultures identified by retrograde labeling with the fluorescent tracer DiI. BDNF and IGF-I promoted neurite outgrowth from ION explants, whereas GDNF and NT-4 had no effect. Injections of NT-4, but not GDNF, in the retina decreased the survival of ION neurons and accelerated cell death in the ION. NT-4-like immunoreactivity was present in the retina and the ION. Exogenous, radiolabeled NT-4, but not GDNF or IGF-I, was retrogradely transported from the retina to the ION. NT-4 transport was significantly reduced by coinjection of excess cold nerve growth factor (NGF), indicating that the majority of NT-4 bound to p75 neurotrophin receptors during axonal transport. Binding of NT-4 to chick p75 receptors was confirmed in L-cells, which express chick p75 receptors. These data indicate that GDNF has no direct trophic effects on ION neurons. IGF-I may be an afferent trophic factor for the ION, and NT-4 may act as an antagonist to BDNF, either by competing with BDNF for p75 and/or trkB binding or by signaling cell death via p75. CI - Copyright 2000 John Wiley & Sons, Inc. FAU - Janiga, T A AU - Janiga TA AD - Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA. FAU - Rind, H B AU - Rind HB FAU - von Bartheld, C S AU - von Bartheld CS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurobiol JT - Journal of neurobiology JID - 0213640 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carrier Proteins) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Receptors, Nerve Growth Factor) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - Animals MH - Apoptosis/drug effects/physiology MH - Axonal Transport/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/*metabolism/*pharmacology MH - Carrier Proteins/drug effects/metabolism MH - Cell Count MH - Cell Survival MH - Cells, Cultured MH - Chick Embryo MH - Glial Cell Line-Derived Neurotrophic Factor MH - Immunoblotting MH - Immunohistochemistry MH - Insulin-Like Growth Factor I/*metabolism/*pharmacology MH - Mesencephalon/*drug effects/embryology/*metabolism MH - Nerve Growth Factors/*metabolism/*pharmacology MH - Nerve Tissue Proteins/drug effects/*metabolism/*pharmacology MH - Neurites/drug effects/metabolism/ultrastructure MH - Receptors, Nerve Growth Factor/drug effects/metabolism MH - Retina/drug effects/embryology/metabolism MH - Superior Colliculi/cytology/drug effects/metabolism MH - Visual Pathways/*drug effects/embryology/*metabolism EDAT- 2000/06/08 09:00 MHDA- 2000/08/01 11:00 CRDT- 2000/06/08 09:00 PHST- 2000/06/08 09:00 [pubmed] PHST- 2000/08/01 11:00 [medline] PHST- 2000/06/08 09:00 [entrez] AID - 10.1002/(SICI)1097-4695(20000605)43:3<289::AID-NEU7>3.0.CO;2-5 [pii] AID - 10.1002/(sici)1097-4695(20000605)43:3<289::aid-neu7>3.0.co;2-5 [doi] PST - ppublish SO - J Neurobiol. 2000 Jun 5;43(3):289-303. doi: 10.1002/(sici)1097-4695(20000605)43:3<289::aid-neu7>3.0.co;2-5.