Critical periods of basic fibroblast growth factor and brain-derived neurotrophic factor in the development of the chicken cochleovestibular ganglion in vitro.
The temporal roles of brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF-2) in the development of sensory neurons have been studied in a cell culture preparation which models normal embryonic inner ear development (normocytic). Previous studies showed that FGF-2 stimulated migration and differentiation of ganglion cells for the first 2 days in vitro, but after 5 days led to degeneration, implicating other factors in their later development. To see if BDNF could be such a factor, otocysts were explanted from white leghorn embryos at the time when ganglion cell precursors normally start migrating from the otic epithelium. Cultures were grown in a defined medium, either with or without human recombinant FGF-2 for 2 days or with BDNF. On Day 3, FGF-2 was replaced either with BDNF in defined medium or with defined medium only. Measurements of neuroblast migration and neurite outgrowth were made by time-lapse imaging in living cultures. In cultures receiving BDNF on Day 3, cell migration and neurite outgrowth from the explant increased for more than 3 weeks but not in cultures receiving only defined medium from Day 3. Cultures did not survive more than 3-4 days when receiving either BDNF in defined medium or defined medium alone from the first day. A neutralizing antibody to BDNF inhibited neuronal migration and neurite outgrowth, and it also blocked the effects of exogenous BDNF. BDNF did not enhance the effects of FGF-2 by interacting with it. These experiments defined a temporal sequence in which FGF-2 acts early in development, while BDNF affects a later stage.
Hossain
W A
WA
Department of Anatomy, University of Connecticut Health Center, Farmington 06030-3405, USA.
Rutledge
A
A
Morest
D K
DK
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D004347:Drug Interactions; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology* / Q000633:toxicity; D017950:Ganglia, Sensory / Q000187:drug effects / Q000196:embryology*; D006801:Humans; D009024:Morphogenesis / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2