A delayed role for nitric oxide-sensitive guanylate cyclases in a migratory population of embryonic neurons.
A delayed role for nitric oxide-sensitive guanylate cyclases in a migratory population of embryonic neurons.
复制标题
DOI：
10.1006/dbio.1998.9066
复制
发表时间：
1998-12
影响因子：
2.7
通讯作者：
J. Wright;K. M. Schwinof;M. Snyder;P. F. Copenhaver
中科院分区：
文献类型：
--
作者：
J. Wright;K. M. Schwinof;M. Snyder;P. F. Copenhaver
神经元分化需要细胞内对不同细胞外刺激的协调反应，但特定信号机制在调节这一过程中的作用仍知之甚少。最近发现可溶性鸟苷酸环化酶 (sGC) 可以被一氧化氮 (NO) 和一氧化碳 (CO) 等可扩散自由基气体刺激产生细胞内信使 cGMP，它在多种胚胎神经元中表达，并参与神经元运动和分化的控制。利用 Manduca sexta 蛾的肠神经系统 (ENS)，我们检查了 NO 和 NO 敏感 sGC 在一组已识别的迁移神经元（EP 细胞）的迁移和分化过程中的作用。迁移开始后不久，一部分 EP 细胞开始表达 NO 敏感的 sGC 活性（用抗 cGMP 抗血清观察）。与中枢神经系统中的许多神经元不同，EP 细胞中 sGC 活性的表达不是短暂的，而是在轴突伸长和肠道肌肉组织末端分支形成的后续阶段持续存在。相比之下，直到突触形成期间，EP 细胞附近的一氧化氮合酶活性（使用 NADPH-心肌黄酶组织化学可视化）才可检测到。旨在改变体内胚胎培养制剂中 sGC 和 NOS 活性的操作对 EP 细胞的迁移或轴突生长没有明显影响。相反，抑制这两种酶会导致迁移后神经元内末端突触分支形成的显着减少。这些结果表明，虽然 NO 敏感的 sGC 活性在 EP 细胞最初的迁移扩散过程中提前表达，但只有在迁移完成后（与成熟突触连接的形成一致）才能很好地证明该信号通路的作用。
Neuronal differentiation requires a coordinated intracellular response to diverse extracellular stimuli, but the role of specific signaling mechanisms in regulating this process is still poorly understood. Soluble guanylate cyclases (sGCs), which can be stimulated by diffusible free radical gasses such as nitric oxide (NO) and carbon monoxide (CO) to produce the intracellular messenger cGMP, have recently been found to be expressed within a variety of embryonic neurons and implicated in the control of both neuronal motility and differentiation. Using the enteric nervous system (ENS) of the moth, Manduca sexta, we examined the role of NO and NO-sensitive sGCs during the migration and differentiation of an identified set of migratory neurons (the EP cells). Shortly after the onset of their migration, a subset of EP cells began to express NO-sensitive sGC activity (visualized with an anti-cGMP antiserum). Unlike many neurons in the central nervous system, the expression of sGC activity in the EP cells was not transient but persisted throughout subsequent periods of axon elongation and terminal branch formation on the gut musculature. In contrast, nitric oxide synthase activity (visualized using NADPH-diaphorase histochemistry) was undetectable in the vicinity of the EP cells until the period of synapse formation. Manipulations designed to alter sGC and NOS activity in an in vivo embryonic culture preparation had no discernible effect on either the migration or axonal outgrowth of the EP cells. In contrast, inhibition of both of these enzymes resulted in a significant reduction in terminal synaptic branch formation within the postmigratory neurons. These results indicate that while NO-sensitive sGC activity is expressed precociously within the EP cells during their initial migratory dispersal, a role for this signaling pathway can only be demonstrated well after migration is complete, coincident with the formation of mature synaptic connections.