Abstract
The neuropeptide calcitonin gene-related peptide (CGRP) expressed by one-third of rat dorsal root ganglion (DRG) neurons mediates pain sensation and vasodilation. The developmental regulation of CGRP is poorly understood, but may involve target-derived factors from skin or viscera. Few embryonic DRG neurons in defined culture express CGRP, indicating inductive signals are required. Follistatin blocked CGRP expression induced by serum or skin-conditioned medium, implicating transforming growth factor beta (TGFbeta) family members. Activin or bone morphogenetic proteins (BMPs) 2, 4, or 6 stimulated CGRP expression in 60% of DRG neurons. Brief BMP4 application supported maximal CGRP induction, suggesting that BMP4 is a "switch" rather than a continuous modulator of neuropeptide phenotype. DRG expressed corresponding receptor subunits and exhibited Smad1 transcription factor nuclear translocation following BMP stimulation. BMP mRNAs were present in embryonic targets innervated by CGRP-expressing neurons. Thus, specific TGFbeta family members are candidate regulators of CGRP expression in sensory neurons.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Activins
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Animals
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Protein 6
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Bone Morphogenetic Protein Receptors
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Bone Morphogenetic Proteins / pharmacology*
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Calcitonin Gene-Related Peptide / biosynthesis
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Calcitonin Gene-Related Peptide / genetics*
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Cells, Cultured
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DNA Primers
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Embryo, Mammalian
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Ganglia, Spinal / cytology
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Ganglia, Spinal / embryology
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Ganglia, Spinal / physiology*
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Gene Expression Regulation / drug effects*
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Inhibins / pharmacology*
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Mice
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Neurons / cytology
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Neurons / drug effects
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Neurons / physiology*
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Polymerase Chain Reaction
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Rats
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Rats, Sprague-Dawley
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Receptors, Cell Surface / metabolism
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Receptors, Growth Factor*
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Transforming Growth Factor beta*
Substances
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Bmp2 protein, mouse
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Bmp2 protein, rat
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Bmp4 protein, mouse
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Bmp4 protein, rat
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Bmp6 protein, mouse
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Bmp6 protein, rat
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Protein 6
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Bone Morphogenetic Proteins
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DNA Primers
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Receptors, Cell Surface
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Receptors, Growth Factor
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Transforming Growth Factor beta
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Activins
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Inhibins
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Bone Morphogenetic Protein Receptors
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Calcitonin Gene-Related Peptide