Activin and bone morphogenetic proteins induce calcitonin gene-related peptide in embryonic sensory neurons in vitro.
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.
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Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4975, USA.
Cappuzzello
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Hall
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D016475:3T3 Cells; D028341:Activins; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D017931:DNA Primers; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007265:Inhibins / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; C525810:Bmp4 protein, mouse; C525811:Bmp4 protein, rat; C525817:Bmp6 protein, mouse; C525818:Bmp6 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D052004:Bone Morphogenetic Protein Receptors; D015740:Calcitonin Gene-Related Peptide