Knockdown of Nav1.6a Na+ channels affects zebrafish motoneuron development
Knockdown of Nav1.6a Na+ channels affects zebrafish motoneuron development
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DOI：
10.1242/dev.02559
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发表时间：
2006-10-01
期刊：
影响因子：
4.6
通讯作者：
Ribera, Angeles B.
中科院分区：
文献类型：
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作者：
Pineda, Ricardo H.;Svoboda, Kurt R.;Ribera, Angeles B.
除了快速的信号传导，电活动还为发育中的神经元提供了重要的线索。电活动依赖于几种不同类型的电压门控离子通道的功能。而电压门控钙通道活性调节神经元分化的几个方面，更少的是已知的电压门控Na+通道，电信号的基本介质的发育作用。在这里，我们专注于斑马鱼Na+通道同种型，Na（v）1.6a，这是由scn 8a基因编码。一组有限的脊髓神经元，包括背侧感觉Rohon-Beard细胞，两个运动神经元亚型与不同的轴突轨迹，在胚胎发育过程中表达scn 8a。CaP是一种早期出生的初级运动神经元亚型，具有腹侧投射的轴突，表达scn 8a，一类次级运动神经元具有背侧投射的轴突。为了测试scn 8a的发育作用，我们使用反义吗啉代敲低Na（v）1.6a蛋白。在表达scn 8a的神经元中，钠通道蛋白和电流幅度降低。此外，Na（v）1.6a敲低改变了一些但不是所有运动神经元的轴突形态。背侧投射的次级运动神经元表达scn 8a并显示延迟的轴突生长。相比之下，CaP轴突发育正常，尽管基因的表达。令人惊讶的是，腹侧投射的次级运动神经元，其中scn 8a未被检测到的人口，显示异常的轴突形态。镶嵌分析表明，对腹侧投射的次级运动神经元的影响是非细胞自主的。因此，电压门控Na+通道在神经元发育过程中起着细胞自主和非细胞自主的作用。
In addition to rapid signaling, electrical activity provides important cues to developing neurons. Electrical activity relies on the function of several different types of voltage-gated ion channels. Whereas voltage-gated Ca2+ channel activity regulates several aspects of neuronal differentiation, much less is known about developmental roles of voltage-gated Na+ channels, essential mediators of electrical signaling. Here, we focus on the zebrafish Na+ channel isotype, Na(v)1.6a, which is encoded by the scn8a gene. A restricted set of spinal neurons, including dorsal sensory Rohon-Beard cells, two motoneuron subtypes with different axonal trajectories, express scn8a during embryonic development. CaP, an early born primary motoneuron subtype with ventrally projecting axons expresses scn8a, as does a class of secondary motoneurons with axons that project dorsally. To test for developmental roles of scn8a, we knocked down Na(v)1.6a protein using antisense morpholinos. Na+ channel protein and current amplitudes were reduced in neurons that express scn8a. Furthermore, Na(v)1.6a knockdown altered axonal morphologies of some but not all motoneurons. Dorsally projecting secondary motoneurons express scn8a and displayed delayed axonal outgrowth. By contrast, CaP axons developed normally, despite expression of the gene. Surprisingly, ventrally projecting secondary motoneurons, a population in which scn8a was not detected, displayed aberrant axonal morphologies. Mosaic analysis indicated that effects on ventrally projecting secondary motoneurons were non cell-autonomous. Thus, voltage-gated Na+ channels play cell-autonomous and non cell-autonomous roles during neuronal development.