Activin and bone morphogenetic proteins induce calcitonin gene-related peptide in embryonic sensory neurons in vitro

Mol Cell Neurosci. 1999 Dec;14(6):506-18. doi: 10.1006/mcne.1999.0798.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Activins
  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Protein Receptors
  • Bone Morphogenetic Proteins / pharmacology*
  • Calcitonin Gene-Related Peptide / biosynthesis
  • Calcitonin Gene-Related Peptide / genetics*
  • Cells, Cultured
  • DNA Primers
  • Embryo, Mammalian
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / embryology
  • Ganglia, Spinal / physiology*
  • Gene Expression Regulation / drug effects*
  • Inhibins / pharmacology*
  • Mice
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology*
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / metabolism
  • Receptors, Growth Factor*
  • Transforming Growth Factor beta*


  • Bmp2 protein, mouse
  • Bmp2 protein, rat
  • Bmp4 protein, mouse
  • Bmp4 protein, rat
  • Bmp6 protein, mouse
  • Bmp6 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Proteins
  • DNA Primers
  • Receptors, Cell Surface
  • Receptors, Growth Factor
  • Transforming Growth Factor beta
  • Activins
  • Inhibins
  • Bone Morphogenetic Protein Receptors
  • Calcitonin Gene-Related Peptide