Bilodeau M L, Boulineau T, Hullinger R L, Andrisani O M
Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Mol Cell Biol. 2000 May;20(9):3004-14. doi: 10.1128/MCB.20.9.3004-3014.2000.
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.
脊椎动物神经嵴细胞（嵴细胞）是研究细胞命运特化的一个非常有价值的模型系统。嵴细胞适合进行组织培养，并且它们能分化为多种神经元和非神经元细胞类型。早期研究已经确定，骨形态发生蛋白（BMP - 2、- 4和- 7）以及能提高细胞内环磷酸腺苷（cAMP）水平的物质，可刺激神经嵴培养物中交感肾上腺（SA，肾上腺素能）谱系的发育。为了研究信号通路之间的相互作用机制是否影响嵴细胞分化，我们对BMP - 2和提高cAMP水平的物质对原代培养的鹌鹑躯干神经嵴细胞发育的联合作用进行了表征。我们报告称，cAMP信号通路调节影响SA细胞发育的正向和负向信号。具体而言，我们发现cAMP信号通路的适度激活与BMP - 2协同促进SA细胞发育以及SA谱系决定基因Phox2a的表达。相比之下，即使存在BMP - 2，cAMP信号通路的强烈激活也会抑制SA细胞发育以及SA谱系决定基因ASH - 1和Phox2的表达。我们得出结论，在神经嵴培养物中，cAMP信号通路作为SA细胞发育的双相调节因子发挥作用。
