Reformation of the dopaminergic nigrostriatal pathway: a role of reeler gene product Reelin

Reeler基因(Reln^&lt；rl&gt；，以前的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基因突变导致一些脑干核团中广泛的板层皮质区域的破坏和异位。在正常小鼠的胚胎纹状体中，已有大量的reelin基因的表达，然而，在小鼠胚胎纹状体中，神经元在基底节的异常定位仍有待研究。我们首次提供了Reelin在黑质发育形成中的潜在作用的证据。在缺乏Reelin的卷轴突变小鼠中，去往黑质的多巴胺能神经元不能横向迁移，而是异常地聚集在腹侧被盖区。它们的轴突似乎投射到形成“多巴胺岛”的纹状体斑块上。来自正常小鼠的结果表明，在胚胎中期，经CR-50鉴定的Reelin在腹侧系膜…中高度集中更多的是头核，黑质的多巴胺能神经元正在进行横向迁移，到达成年大脑的最终位置。结合CR-50标记和轴突顺行追踪，证明胚胎纹状体神经元可能通过轴突投射向中脑腹侧部分供应Reelin。我们假设Reelin在黑质多巴胺能神经元的定位中起作用，它可以通过跨轴突传递系统在远离其出生地的偏远位置作为环境线索。大脑皮层被组织成水平和垂直的神经元阵列及其纤维连接，形成解剖和生理上不同的板层和柱状室。然而，这种二分模式背后的发育机制(S)仍然是一个谜。我们提供的解剖学证据表明，Reelin是一种由Cajal-Retzius细胞产生和分泌的可扩散蛋白，参与了小鼠丘前皮质垂直细胞结构的发育形成，在出生后早期，皮质板状神经元及其树突的垂直柱状排列清晰可见。我们的结果还表明，Reelin通过作为皮质板神经元及其树突延伸的抑制或停止信号，在这些垂直结构的形成中发挥作用。除了水平板层受到干扰外，缺乏Reelin的卷轴突变小鼠还表现出这些垂直结构的破坏。根据目前的发现，我们假设Reelin和Cajal-Retzius细胞不仅调控大脑皮层水平板层结构的发育形成，而且还调控垂直柱状结构的发育形成。较少

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 mid-embryonic stage, Reelin identified with CR-50 is highly concentrated in the ventral mesenc … More ephalon, 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.The cerebral cortex is organized into horizontal and vertical arrays of neurons and their fiber connections that form anatomically and physiologically distinct laminar and columnar compartments. However, the developmental mechanism(s) underlying this dichotomous pattern remains a mystery. We provide anatomical evidence suggesting that Reelin, a diffusible protein produced and secreted by Cajal-Retzius cells, is involved in the developmental formation of the vertical cell structures in the mouse presubicular cortex, the unique site where the vertical columnar arrays of cortical plate neurons and their dendritic branches are clearly identified during the early postnatal period. Our results also suggest that Reelin plays a role in the formation of these vertical structures by acting as an inhibitory or stop signal for cortical plate neurons and their dendritic extensions. In addition to having perturbed horizontal laminae, reeler mutant mice lacking of Reelin display disruption of these vertical structures. Based on the present findings, we hypothesize that Reelin and Cajal-Retzius cells regulate the developmental formation of not only horizontal laminations but also vertical columnar structures in the cerebral cortex. Less