Role of neuropilin‐2 in the ipsilateral growth of midbrain dopaminergic axons
Role of neuropilin‐2 in the ipsilateral growth of midbrain dopaminergic axons
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DOI：
10.1111/ejn.12190
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发表时间：
2013-05
影响因子：
3.4
通讯作者：
Makio Torigoe;Kenta Yamauchi;A. Tamada;I. Matsuda;A. Aiba;V. Castellani;F. Murakami
中科院分区：
文献类型：
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作者：
Makio Torigoe;Kenta Yamauchi;A. Tamada;I. Matsuda;A. Aiba;V. Castellani;F. Murakami
中枢神经系统的轴突投射可分为交叉或非交叉。轴突的交叉和不交叉可以用中线结构分泌的吸引和排斥分子如Netrin - 1和Slits来解释。然而，即使在slit1和slit2或roundabout1 （robo1）和robo2这两种Slits受体的双敲除小鼠中，也可以建立非交叉投射。在这里，我们发现一种由Neuropilin‐2 （Nrp2）介导的新机制有助于中脑多巴胺能神经元（mdan）的非交叉突起的形成。在mDAN的一个亚群中检测到Nrp2的转录活性，其蛋白在通过同侧间脑生长的mDAN轴突中表达。在nrp2lacZ/lacZ小鼠中，mDAN轴突向腹中线方向异常生长，甚至越过腹中线，提示Nrp2对于mDAN同侧突起的发展是必要的。我们通过分析单敲除或双敲除小鼠的mDAN轴突轨迹，研究了信号蛋白3B （Sema3B）和Sema3F这两种Nrp2配体的参与。在这两种情况下，mDAN轴突仍然是同侧的，这表明参与机制独立于这些Sema3s。Nrp2‐缺陷的mDAN轴突保留了对Slit2的响应性，这表明nrp2lacZ/lacZ小鼠中mDAN轴突的异常不是由Slit/Robo信号的改变间接介导的。综上所述，我们的研究结果表明Nrp2介导的一种新机制有助于mDAN轴突非交叉投射的建立。
Axonal projections in the CNS can be categorized as either crossed or uncrossed. Crossing and uncrossing of axons has been explained by attractive and repulsive molecules like Netrin‐1 and Slits, which are secreted by midline structures. However, uncrossed projections can be established even in double knockout mice of slit1 and slit2 or of roundabout1 (robo1) and robo2, two receptors for Slits. Here, we found that a novel mechanism mediated by Neuropilin‐2 (Nrp2) contributes to the formation of uncrossed projections of midbrain dopaminergic neurons (mDANs). Nrp2 transcriptional activities were detected in a subset of mDANs, and its protein was expressed in mDAN axons growing through the ipsilateral diencephalon. In nrp2lacZ/lacZ mice, mDAN axons aberrantly grew toward the ventral midline and even crossed it, suggesting that Nrp2 is necessary for the development of mDAN ipsilateral projections. We investigated the involvement of Semaphorin 3B (Sema3B) and Sema3F, two ligands of Nrp2, by analysing mDAN axon trajectories in single or double knockout mice. In both cases, mDAN axons still projected ipsilaterally, suggesting the involvement mechanisms independent of these Sema3s. Nrp2‐deficient mDAN axons retained their responsiveness to Slit2, demonstrating that aberrant mDAN axons in nrp2lacZ/lacZ mice were not indirectly mediated by alterations in Slit/Robo signaling. Taken together, our results indicate that a novel mechanism mediated by Nrp2 contributes to the establishment of uncrossed projections by mDAN axons.