Neuropilin-1la is involved in trunk motor axon outgrowth in embryonic zebrafish
Neuropilin-1la is involved in trunk motor axon outgrowth in embryonic zebrafish
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DOI：
10.1002/dvdy.20520
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发表时间：
2005-11-01
影响因子：
2.5
通讯作者：
Becker, CG
中科院分区：
文献类型：
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作者：
Feldner, J;Becker, T;Becker, CG
神经纤毛蛋白-1是轴突排斥性信号蛋白和血管内皮生长因子（VEGF）的受体，在血管生成和轴突生长中发挥作用。在这里，我们显示强烈的表达neuropilin-la在初级运动神经元在胚胎斑马鱼的躯干。使用反义吗啉代寡核苷酸减少神经毡蛋白-la的表达诱导运动神经的异常分支、运动神经从脊髓的额外出口点以及神经元以剂量依赖性方式沿沿着运动轴突途径迁移出脊髓。这些表型可以通过共注射neuropilin-la mRNA部分挽救。脊髓和头部的其他轴突似乎不受吗啉代治疗的影响。此外，neuropilin-la morpholino治疗扰乱了受精后24小时胚胎躯干中血管的正常形成，如微血管造影所示。吗啉代VEGF也扰乱了血管的形成，但不影响运动轴突，表明血管的正确形成是不需要初级运动轴突的生长。与semaphorin 3A同源的semaphorin 3A 1和semaphorin 3A 2的吗啉代也对运动轴突的生长没有影响。然而，联合注射neuropilin-la morpholino，浓度不引起轴突畸变时，单独注射，与VEGF，脑信号蛋白3A 1，或脑信号蛋白3A 2 morpholinos协同增加的比例显示异常运动轴突生长的胚胎。因此，在初级运动神经元中的neuropilin-la可以整合来自几个配体的信号，并且是斑马鱼中初级运动神经的适当节段性生长所需要的。
Neuropilin-1, a receptor for axon-repellent semaphorins and vascular endothelial growth factor (VEGF), functions both in angiogenesis and axon growth. Here, we show strong expression of neuropilin-la in primary motor neurons in the trunk of embryonic zebrafish. Reducing the expression of neuropilin-la using antisense morpholino oligonucleotides induced aberrant branching of motor nerves, additional exit points of motor nerves from the spinal cord, and migration of neurons out of the spinal cord along the motor axon pathway in a dose-dependent manner. These phenotypes could be partially rescued by coinjecting neuropilin-la mRNA. Other axons in the spinal cord and head appeared unaffected by the morpholino treatment. In addition, neuropilin-la morpholino treatment disturbed normal formation of blood vessels in the trunk of 24 hours postfertilization embryos, as shown by microangiography. Morpholinos to VEGF also disturbed formation of blood vessels but did not affect motor axons, indicating that correct formation of blood vessels is not needed for the growth of primary motor axons. Morpholinos to the semaphorin 3A homologs semaphorin 3A1 and semaphorin 3A2 also had no effect on motor axon growth. However, combined injections of neuropilin-la morpholino, at a concentration that did not elicit axonal aberrations when injected alone, with VEGF, semaphorin 3A1, or semaphorin 3A2 morpholinos synergistically increased the proportion of embryos showing aberrant motor axon growth. Thus, neuropilin-la in primary motor neurons may integrate signals from several ligands and is needed for proper segmental growth of primary motor nerves in zebrafish.