Depolarization differentially regulates the effects of bone morphogenetic protein (BMP)-2, BMP-6, and activin A on sympathetic neuronal phenotype.
As a first step in defining the role of the transforming growth factor-beta (TGF-beta) superfamily in the development of the sympathetic nervous system, we analyzed effects of several members of this family on neuronal gene expression in dissociated cell culture using a reverse transcription-polymerase chain reaction method. We found that, in addition to activin A, bone morphogenetic protein (BMP)-2 and BMP-6 also induce mRNAs for distinct sets of neuropeptides and neurotransmitter synthetic enzymes in sympathetic neurons. TGF-beta 1 and TGF-beta 3 are, however, without detectable effect in this assay. Surprisingly, we find that the patterns of neuropeptide genes induced by activin A, BMP-2, and BMP-6 are each affected differently by neuronal depolarization. Depolarization can either promote or block the effects of different cytokines on the same neuropeptide gene, and depolarization can either promote or block the effects of a given cytokine on different neuropeptide genes. This evidence suggests that neuronal activity may be a key mediator of cytokine modulation of neuronal gene expression.
Biology Division, California Institute of Technology, Pasadena 91125.
M J
MJ
Fann
P H
PH
Patterson
D028341:Activins; D000818:Animals; D019485:Bone Morphogenetic Proteins; D004594:Electrophysiology; D015870:Gene Expression / Q000187:drug effects*; D007265:Inhibins / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics*; D018377:Neurotransmitter Agents / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000166:cytology* / Q000254:growth & development
D019485:Bone Morphogenetic Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D011506:Proteins; D012333:RNA, Messenger; D028341:Activins; D007265:Inhibins