Neurotransmitter phenotype-specific expression changes in developing sympathetic neurons.
During late developmental phases individual sympathetic neurons undergo a switch from noradrenergic to cholinergic neurotransmission. This phenomenon of plasticity depends on target-derived signals in vivo and is triggered by neurotrophic factors in neuronal cultures. To analyze genome-wide expression differences between the two transmitter phenotypes we employed DNA microarrays. RNA expression profiles were obtained from chick paravertebral sympathetic ganglia, treated with neurotrophin 3, glial cell line-derived neurotrophic factor or ciliary neurotrophic factor, all of which stimulate cholinergic differentiation. Results were compared with the effect of nerve growth factor, which functions as a pro-noradrenergic stimulus. The gene set common to all three comparisons defined the noradrenergic and cholinergic synexpression groups. Several functional categories, such as signal transduction, G-protein-coupled signaling, cation transport, neurogenesis and synaptic transmission, were enriched in these groups. Experiments based on the prediction that some of the identified genes play a role in the neurotransmitter switch identified bone morphogenetic protein signaling as an inhibitor of cholinergic differentiation.
Apostolova
Galina
G
Institute for Neuroscience, Innsbruck Medical University, MZA, Anichstrasse 35, 6020 Innsbruck, Austria.
Dorn
Roland
R
Ka
Sojeong
S
Hallböök
Finn
F
Lundeberg
Joakim
J
Liser
Keren
K
Hakim
Vicky
V
Brodski
Claude
C
Michaelidis
Theologos M
TM
Dechant
Georg
G
D000818:Animals; D002642:Chick Embryo; D005728:Ganglia, Sympathetic / Q000166:cytology* / Q000196:embryology*; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017403:In Situ Hybridization / Q000379:methods; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009924:Organ Culture Techniques; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D018377:Neurotransmitter Agents; D012333:RNA, Messenger