Ai X, Cappuzzello J, Hall A K
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4975, USA.
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.
三分之一的大鼠背根神经节（DRG）神经元所表达的神经肽降钙素基因相关肽（CGRP）介导痛觉和血管舒张。人们对CGRP的发育调控了解甚少，但可能涉及来自皮肤或内脏的靶源性因子。在特定培养条件下，很少有胚胎DRG神经元表达CGRP，这表明需要诱导信号。卵泡抑素可阻断血清或皮肤条件培养基诱导的CGRP表达，这意味着转化生长因子β（TGFβ）家族成员参与其中。激活素或骨形态发生蛋白（BMP）2、4或6可刺激60%的DRG神经元表达CGRP。短暂应用BMP4可支持最大程度的CGRP诱导，这表明BMP4是神经肽表型的“开关”而非持续调节剂。DRG表达相应的受体亚基，并在BMP刺激后表现出Smad1转录因子的核转位。BMP mRNA存在于由表达CGRP的神经元支配的胚胎靶组织中。因此，特定的TGFβ家族成员是感觉神经元中CGRP表达的候选调节因子。
