Repulsion and attraction of axons by Semaphorin3D are mediated by different neuropilins in vivo
Repulsion and attraction of axons by Semaphorin3D are mediated by different neuropilins in vivo
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DOI：
10.1523/jneurosci.2349-04.2004
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发表时间：
2004-09-29
影响因子：
5.3
通讯作者：
Halloran, MC
中科院分区：
文献类型：
--
作者：
Wolman, MA;Liu, Y;Halloran, MC
已知3类信号蛋白排斥和/或有时吸引轴突；然而，它们在体内中枢神经系统中引导轴突发育的作用仍然是未知的。我们研究了信号蛋白3d （Sema3D）在斑马鱼中枢神经系统早期轴突通路形成中的作用。Morpholino敲除表明Sema3D对于两条早期轴突通路的正确形成至关重要。Sema3D似乎通过排斥力和束化调节来引导内侧纵束核轴突。相反，Sema3D似乎对形成前连合（AC）的端脑神经元有吸引力。Neuropilin-1A （Npn-1A）的敲除表现了Sema3D敲除对核mlf轴突的影响，而Npn-1A或Npn-2B的敲除表现了AC缺陷。此外，同时部分敲除实验表明Sema3D、Npn-1A和Npn-2B之间存在遗传相互作用。总之，这些数据支持Sema3D可能通过含有Npn-1A的受体作为驱避剂，并通过含有Npn-1A和Npn-2B的受体作为引诱剂的假设。
Class 3 semaphorins are known to repel and/or sometimes attract axons; however, their role in guiding developing axons in the CNS in vivo is still essentially unknown. We investigated the role of Semaphorin3D (Sema3D) in the formation of the early axon pathways in the zebrafish CNS. Morpholino knock-down shows that Sema3D is essential for the correct formation of two early axon pathways. Sema3D appears to guide axons of the nucleus of the medial longitudinal fasciculus (nucMLF) by repulsion and modulation of fasciculation. In contrast, Sema3D appears to be attractive to telencephalic neurons that form the anterior commissure (AC). Knock-down of Neuropilin-1A (Npn-1A) phenocopied the effects of Sema3D knock-down on the nucMLF axons, and knock-down of either Npn-1A or Npn-2B phenocopied the defects of the AC. Furthermore, simultaneous partial knock-down experiments demonstrated genetic interactions among Sema3D, Npn-1A, and Npn-2B. Together, these data support the hypothesis that Sema3D may act as a repellent through receptors containing Npn-1A and as an attractant via receptors containing Npn-1A and Npn-2B.