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首页> 美国卫生研究院文献>Molecular and Cellular Biology >Cyclic AMP Signaling Functions as a Bimodal Switch in Sympathoadrenal Cell Development in Cultured Primary Neural Crest Cells
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Cyclic AMP Signaling Functions as a Bimodal Switch in Sympathoadrenal Cell Development in Cultured Primary Neural Crest Cells

机译：循环AMP信号传导在培养的原代神经C细胞的交感肾上腺细胞发育中起双峰转换的作用。

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摘要

Cells of the vertebrate neural crest (crest cells) are an invaluable model system to address cell fate specification. Crest cells are amenable to tissue culture, and they differentiate to a variety of neuronal and nonneuronal cell types. Earlier studies have determined that bone morphogenetic proteins (BMP-2, -4, and -7) and agents that elevate intracellular cyclic AMP (cAMP) stimulate the development of the sympathoadrenal (SA, adrenergic) lineage in neural crest cultures. To investigate whether interactive mechanisms between signaling pathways influence crest cell differentiation, we characterized the combinatorial effects of BMP-2 and cAMP-elevating agents on the development of quail trunk neural crest cells in primary culture. We report that the cAMP signaling pathway modulates both positive and negative signals influencing the development of SA cells. Specifically, we show that moderate activation of cAMP signaling promotes, in synergy with BMP-2, SA cell development and the expression of the SA lineage-determining gene Phox2a. By contrast, robust activation of cAMP signaling opposes, even in the presence of BMP-2, SA cell development and the expression of the SA lineage-determining ASH-1 and Phox2 genes. We conclude that cAMP signaling acts as a bimodal regulator of SA cell development in neural crest cultures.
机译：脊椎动物神经c的细胞（rest细胞）是解决细胞命运规范的宝贵模型系统。 rest细胞适合组织培养，并且可以分化为多种神经元和非神经元细胞类型。较早的研究已经确定，骨形态发生蛋白（BMP-2，-4和-7）和提高细胞内环AMP（cAMP）的药物可刺激神经rest培养物中交感肾上腺（SA，肾上腺素）谱系的发育。若要调查信号通路之间的相互作用机制是否影响c细胞分化，我们表征了BMP-2和cAMP增强剂在鹌鹑主干神经rest细胞发育中的组合作用。我们报告说，cAMP信号通路调节影响SA细胞发展的正信号和负信号。具体而言，我们表明，与BMP-2协同作用，适度激活cAMP信号传导可促进SA细胞发育和SA谱系决定基因Phox2a的表达。相比之下，即使存在BMP-2，SA细胞发育以及SA谱系决定ASH-1和Phox2基因的表达，cAMP信号的强烈激活也遭到反对。我们得出结论，cAMP信号传导在神经c文化中充当SA细胞发育的双峰调节器。

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