Division of Cell Biology, Institute of Physiology, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, Hannover, Germany.
Cell Mol Life Sci. 2011 Jun;68(12):2089-99. doi: 10.1007/s00018-010-0554-9. Epub 2010 Oct 19.
Neuronal migration is one of the most critical processes during early brain development. The gaseous messenger nitric oxide (NO) has been shown to modulate neuronal and glial migration in various experimental models. Here, we analyze a potential role for NO signaling in the migration of fetal human neural progenitor cells. Cells migrate out of cultured neurospheres and differentiate into both neuronal and glial cells. The neurosphere cultures express neuronal nitric oxide synthase and soluble guanylyl cyclase that produces cGMP upon activation with NO. By employing small bioactive enzyme activators and inhibitors in both gain and loss of function experiments, we show NO/cGMP signaling as a positive regulator of migration in neurosphere cultures of early developing human brain cells. Since NO signaling regulates cell movements from developing insects to mammalian nervous systems, this transduction pathway may have evolutionary conserved functions.
神经元迁移是大脑早期发育过程中最重要的过程之一。气态信使一氧化氮(NO)已被证明可调节各种实验模型中的神经元和神经胶质细胞迁移。在这里,我们分析了 NO 信号在人胎脑神经祖细胞迁移中的潜在作用。细胞从培养的神经球中迁移出来并分化为神经元和神经胶质细胞。神经球培养物表达神经元型一氧化氮合酶和可溶性鸟苷酸环化酶,当与 NO 激活时会产生 cGMP。通过在功能增益和功能丧失实验中使用小的生物活性酶激活剂和抑制剂,我们表明 NO/cGMP 信号作为早期发育人脑细胞神经球培养物中迁移的正调节剂。由于 NO 信号调节从发育中的昆虫到哺乳动物神经系统的细胞运动,因此这种转导途径可能具有进化保守的功能。