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-β (TGF-β) 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-β1 and TGF-β3 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.
© 1994 International Society for Neurochemistry. Resubmitted manuscript received May 24, 1994; accepted June 3, 1994. We thank Doreen McDowell for help with tissue culture materials and Drs. David Shelton and John M. Wozney for providing cytokines. We thank Drs. Lisa Banner and Zaven Kaprielian for comments on the manuscript. This project was supported by grants from NINDS (Javits Neuroscience Investigator Award) to P.H.P., as well as a Fellowship from the Ministry of Education, Taiwan, R.O.C., to M.-J.-F.