title: TrkB expression and early sensory neuron survival are independent of endogenous BDNF.
abstract: Sensory neurons initially survive independently of neurotrophins in culture during the stage of development when their axons are growing to their targets. Because mRNAs encoding brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB are detectable in subsets of sensory neurons from the earliest stages of their development, we investigated whether a BDNF autocrine loop is responsible for sustaining the survival of these neurons during this early stage in their development. Low-density dissociated cultures of nodose and dorsal root ganglion neurons were established from wild type and BDNF(-/-) mouse embryos at this stage and were grown in defined medium without added neurotrophins. Wild type and BDNF-deficient neurons survived equally well under these conditions, indicating that a BDNF autocrine loop does not play a role in sustaining the survival of sensory neurons during the earliest stages of their development. As sensory axons approach their targets, TrkB expression increases in a subset of neurons that becomes dependent on BDNF produced by other cells. Because numerous studies have shown that neurotrophins, including BDNF, increase expression of their receptors, we investigated whether endogenous BDNF is required for the increase in TrkB expression observed during stage of development. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the developmental increase in TrkB mRNA expression occurred normally in the sensory ganglia of BDNF(-/-) embryos. Taken together, our studies of sensory neuron development in BDNF-deficient embryos have demonstrated that endogenous BDNF is neither required for the early survival of these neurons nor for the induction of TrkB expression.
authors.affiliation: School of Biomedical Sciences, Biomedical Building, University of St. Andrews, St. Andrews, Fife, Scotland.
authors.forename: K
authors.initials: K
authors.lastname: Huber
authors.forename: F
authors.initials: F
authors.lastname: Kuehnel
authors.forename: S
authors.initials: S
authors.lastname: Wyatt
authors.forename: A M
authors.initials: AM
authors.lastname: Davies
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020813:Receptor, trkB