PMID- 12009766 OWN - NLM STAT- MEDLINE DCOM- 20020523 LR - 20091119 IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 175 IP - 1 DP - 2002 May TI - Sequential interactions of fibroblast growth factor-2, brain-derived neurotrophic factor, neurotrophin-3, and their receptors define critical periods in the development of cochlear ganglion cells. PG - 138-51 AB - We studied the interactions of neurotrophin-3 (NT3) with brain-derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF-2), and their effects on tyrosine kinase C (TrkC) expression during cochlear ganglion development. Otocysts were explanted from white leghorn chicken embryos at stages when the neuronal precursors normally start to migrate. Cultures were fed with various combinations of NT3, BDNF, and FGF-2. NT3 appeared to have a greater effect on neurite outgrowth than on migration and was enhanced by BDNF. The results from in situ hybridization and immunostaining for TrkC receptor revealed up-regulation of the mRNA and protein by combining NT-3 and BDNF. NT-3 combined with FGF-2 produced down-regulation of receptor. Neutralizing antibody to NT3 had an inhibitory effect on neuronal development, suggesting that endogenous NT3 is normally active during the period examined. The findings suggest an interactive role of NT3 in early neuronal development. The trophic synergism of NT3 and BDNF may result from up-regulation of TrkC. This hypothesis is consistent with immunostaining in the embryonic basilar papilla, which localized TrkC to the initial axonal invasion sites. While the growth factors each produce particular trophic effects, the interactions of these factors define a critical sequence of developmental events based on modulation of receptor expression. CI - Copyright 2002 Elsevier Science (USA). FAU - Hossain, W Amin AU - Hossain WA AD - Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030-3401, USA. FAU - Brumwell, C L AU - Brumwell CL FAU - Morest, D K AU - Morest DK LA - eng GR - R01NS29613/NS/NINDS NIH HHS/United States GR - T32DC00025/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Antibodies, Blocking) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neurotrophin 3) RN - 0 (RNA, Messenger) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - EC 2.7.10.1 (Receptor, trkC) SB - IM MH - Animals MH - Antibodies, Blocking/pharmacology MH - Brain-Derived Neurotrophic Factor/pharmacology/*physiology MH - Cell Movement/drug effects MH - Cells, Cultured MH - Chick Embryo MH - Drug Interactions/physiology MH - Fibroblast Growth Factor 2/pharmacology/*physiology MH - Immunohistochemistry MH - In Situ Hybridization MH - Neurites/drug effects MH - Neurons/cytology/drug effects MH - Neurotrophin 3/antagonists & inhibitors/pharmacology/*physiology MH - RNA, Messenger/metabolism MH - Receptor, trkC/genetics/*metabolism MH - Spiral Ganglion/cytology/drug effects/*embryology/physiology MH - Stem Cells/cytology/drug effects MH - Time Factors EDAT- 2002/05/16 10:00 MHDA- 2002/05/25 10:01 CRDT- 2002/05/16 10:00 PHST- 2002/05/16 10:00 [pubmed] PHST- 2002/05/25 10:01 [medline] PHST- 2002/05/16 10:00 [entrez] AID - S0014488602978726 [pii] AID - 10.1006/exnr.2002.7872 [doi] PST - ppublish SO - Exp Neurol. 2002 May;175(1):138-51. doi: 10.1006/exnr.2002.7872.