Activin and bone morphogenetic proteins induce calcitonin gene-related peptide in embryonic sensory neurons in vitro
Molecular and Cellular Neurosciences
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 β (TGFβ) 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 TGFβ family members are candidate regulators of CGRP expression in sensory neurons.
Ai, X., Cappuzzello, J., & Hall, A. (1999). Activin and bone morphogenetic proteins induce calcitonin gene-related peptide in embryonic sensory neurons in vitro. Molecular and Cellular Neurosciences, 14 (6). http://dx.doi.org/10.1006/mcne.1999.0798