Distinct Roles of Neuropilin 1 Signaling for Radial and Tangential Extension of Callosal Axons
Distinct Roles of Neuropilin 1 Signaling for Radial and Tangential Extension of Callosal Axons
复制标题
DOI：
10.1002/cne.22021
复制
发表时间：
2009-05-20
影响因子：
2.5
通讯作者：
Masu, Masayuki
中科院分区：
文献类型：
--
作者：
Hatanaka, Yumiko;Matsumoto, Tomoko;Masu, Masayuki
皮层兴奋性神经元从其起源的脑室区（VZ）向软膜表面迁移。在迁移过程中，这些神经元在中间区（IZ）表现出星状形状，转化为双极细胞，然后开始放射状迁移，延伸拖尾过程，这可能导致轴突。在这里，我们研究了神经纤毛蛋白1（NRP 1）在这些发育事件中的作用。NRP 1 mRNA和蛋白在IZ中高度表达，星状细胞位于IZ中。Dil标记实验表明，神经元迁移正常发生在Nrp 1突变小鼠胚胎天（E）14.5，突变体生存的最后一天，只有轻微的轴突去束。然而，干扰Nrp 1信号在后期引起寻路错误：当一个显性负形式的Nrp 1被电穿孔到皮质VZ细胞在E12.5或E15.5和围产期检查，发现在切向轴突延伸向中线的指导错误。与此相反，没有显着的影响，注意到皮层兴奋性神经元的迁移。这些研究结果表明，NRP 1起着重要的作用，在指导胼胝体轴突起源于皮层兴奋性神经元，但不支持其迁移的作用。此外，只要皮质板内的径向轴突延伸不受影响，目前的研究结果意味着皮质板内的兴奋性神经元的轴突延伸的分子机制是不同的那些在白色的问题。神经学比较杂志514：215-225，2009. (C)2009 Wiley-Liss，Inc.
Cortical excitatory neurons migrate from their origin in the ventricular zone (VZ) toward the pial surface. During migration, these neurons exhibit a stellate shape in the intermediate zone (IZ), transform into bipolar cells, and then initiate radial migration, extending a trailing process, which may lead to an axon. Here we examined the role of neuropilin 1 (NRP1) in these developmental events. Both NRP1 mRNA and protein were highly expressed in the IZ, where stellate-shaped cells were located. Dil labeling experiments showed that neuronal migration occurred normally in Nrp1 mutant mice up to embryonic day (E) 14.5, the latest day to which the mutant survives, with only subtle axonal defasciculation. However, interference with Nrp1 signaling at a later stage caused pathfinding errors: when a dominant negative form of Nrp1 was electroporated into the cortical VZ cells at E12.5 or E15.5 and examined perinatally, guidance errors were found in tangential axonal extension toward the midline. In contrast, no significant effect was noted on the migration of cortical excitatory neurons. These findings indicate that NRP1 plays an important role in the guidance of callosal axons originating from cortical excitatory neurons but does not support a role in their migration. Moreover, insofar as radial axonal extension within the cortical plate was unaffected, the present findings imply that molecular mechanisms for the axonal extension of excitatory neurons within the cortical plate are distinct from those in the white matter. J. Comp. Neurol. 514:215-225, 2009. (C) 2009 Wiley-Liss, Inc.