Neurotransmitter phenotype-specific expression changes in developing sympathetic neurons

Mol Cell Neurosci. 2007 Jul;35(3):397-408. doi: 10.1016/j.mcn.2007.03.014. Epub 2007 Apr 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chick Embryo
  • Ganglia, Sympathetic / cytology*
  • Ganglia, Sympathetic / embryology*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Developmental / physiology*
  • In Situ Hybridization / methods
  • Neurons / physiology*
  • Neurotransmitter Agents / genetics
  • Neurotransmitter Agents / metabolism*
  • Oligonucleotide Array Sequence Analysis / methods
  • Organ Culture Techniques
  • Phenotype*
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • Neurotransmitter Agents
  • RNA, Messenger