Lack of Reelin causes malpositioning of nigral dopaminergic neurons:: Evidence from comparison of normal and Relnrl mutant mice
Lack of Reelin causes malpositioning of nigral dopaminergic neurons:: Evidence from comparison of normal and Relnrl mutant mice
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DOI：
10.1002/cne.10610
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发表时间：
2003-06-23
影响因子：
2.5
通讯作者：
Ushio, Y
中科院分区：
文献类型：
--
作者：
Nishikawa, S;Goto, S;Ushio, Y
Reeler基因（Reln（rl），以前称为rl）产物Reelin控制神经元的迁移和定位，从而在大脑发育中发挥关键作用。Reln基因突变可导致皮质层状区广泛破坏和脑干部分核团异位。在胚胎的纹状体里。在正常小鼠中，大量的reelin mRNA表达已被证实;然而，在reeler小鼠基底神经节中神经元的异常定位仍有待研究。我们提供了第一个证据的一个潜在的作用，Reelin在黑质的发育形成。在缺乏Reelin的reeler突变小鼠中，去往黑质的多巴胺能神经元不能侧向迁移，并在腹侧被盖区的侧面聚集。它们的轴突似乎投射到纹状体斑块上，形成“多巴胺岛”。“正常小鼠的结果表明，在胚胎中期，用CR-50识别的Reelin高度集中在腹侧中脑，其中黑质多巴胺能神经元正在侧向迁移到成年大脑的最终位置。CR-50标记和顺行轴突追踪的组合提供的证据表明，胚胎纹状体神经元可能通过其轴突投射供应中脑腹侧部分的Reelin。我们假设，Reelin在黑质多巴胺能神经元的定位中起作用，并且它可以通过transaxonal传递系统在远离其出生地的远程站点作为环境提示。
The reeler gene (Reln(rl), formerly rl) product Reelin controls neuronal migration and positioning and thereby plays a key role in brain development. Mutation of Reln leads to widespread disruption of laminar cortical regions and ectopia in some brainstem nuclei. In the embryonic striatum. of normal mice, a substantial expression of reelin mRNA has been documented; however, the anomalous positioning of neurons in the basal ganglia of reeler mice remains to be studied. We provide first evidence for a potential role of Reelin in the developmental formation of the substantia nigra. In reeler mutant mice lacking Reelin, dopaminergic neurons destined for the substantia nigra fail to migrate laterally and become anomalously clustered just lateral to the ventral tegmental area. Their axons appear to project to striatal patches forming "dopamine islands." Results from the normal mice show that, at the midembryonic stage, Reelin identified with CR-50 is highly concentrated in the ventral mesencephalon, where nigral dopaminergic neurons are in progress to migrate laterally to their eventual position of the adult brain. A combination of CR-50 labeling and anterograde axonal tracing provided evidence that embryonic striatal neurons may supply the ventral portion of the mesencephalon with Reelin through their axonal projections. We hypothesize that Reelin plays a role in the positioning of nigral dopaminergic neurons and that it can act as an environmental cue at a remote site far from its birthplace via a transaxonal delivery system.