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Neurotrophins promote neuronal survival by signalling through Trk receptor tyrosine kinases: nerve growth factor signals through TrkA, brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)4 through TrkB and NT3 through TrkC. Although studies in some, but not all, cell lines indicate that NT3 can also signal through TrkA and TrkB, it is not known if such signalling can occur in neurons. We show that NT3 can promote the in vitro survival of sensory and sympathetic neurons isolated from embryos that are homozygous for a null mutation in the trkC gene. During the mid-embryonic period, NT3 promoted the survival of as many trigeminal and nodose neurons as the preferred neurotrophins, NGF and BDNF. However, later in development, these neurons lost their ability to respond to NT3. NT3 also promoted the survival of almost all sympathetic neurons, but no decrease in effectiveness was observed during development. Trigeminal neurons from trkC-/- trkA-/- embryos did not respond to NT3 and nodose neurons from trkB-/- embryos likewise failed to respond to NT3. These results show that NT3 can signal through TrkA and TrkB in neurons at certain stages of development and may explain why the phenotype of NT3-/- mice is more severe than that of trkC-/- mice.

Type

Journal article

Journal

EMBO J

Publication Date

15/09/1995

Volume

14

Pages

4482 - 4489

Keywords

Age Factors, Animals, Cell Survival, Cells, Cultured, Dose-Response Relationship, Drug, Ganglia, Sympathetic, Membrane Proteins, Mice, Mice, Mutant Strains, Nerve Growth Factors, Neurons, Neurotrophin 3, Nodose Ganglion, Peripheral Nervous System, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Receptor, Ciliary Neurotrophic Factor, Receptor, trkA, Receptor, trkC, Receptors, Nerve Growth Factor, Signal Transduction, Trigeminal Ganglion