Role of neuronal migration for the formation of neuronal connections

苔藓纤维投射的小脑前神经元（PCN）的发展提出了一个经典的例子，切向神经元迁移。在PCN中，脑桥神经元遵循刻板的前腹定向通路形成脑桥中的脑桥核。决定PCN边缘迁移和脑桥神经元前迁移的指导机制知之甚少。在这里，我们报告说，来自脑膜组织的趋化因子SDF 1调节PCN的迁移途径。PCN被脑膜组织化学吸引，这是一种由SDF 1源模拟的效应。对Sdf 1受体Cxcr 4基因敲除小鼠的分析表明，PCN的边缘迁移和脑桥神经元的前迁移都被破坏。我们进一步发现，SDF 1/CXCR 4信号传导调节这两个过程的细胞自主。由于破坏神经元迁移，脑桥核形成是高度异常的，存在多个异位脑桥集群后方。异位脑桥簇导致皮质脊髓束形成异位侧支分支。我们的研究结果共同证明了SDF 1/CXCR 4在PCN迁移的多个方面的关键作用，并强调了脱轨迁移对正确核形成的有害后果。此外，我们提供了第一个在体内的证据，脑桥神经元本身诱导侧支从皮质脊髓轴突。

The development of mossy-fibre projecting precerebellar neurons (PCN) presents a classical example of tangential neuronal migration. Among the PCN, the pontine neurons follow a stereotypic anteroventral-directed pathway to form the pontine nuclei in the pons. The guidance mechanisms that determine the marginal migration of PCN and the anterior migration of pontine neurons are poorly understood. Here, we report that a chemokine SDF1 derived from the meningeal tissue regulates the migratory pathways of PCN. PCN are chemoattracted by the meningeal tissue, an effect that is mimicked by an SDF1 source. Analysis of knockout mice for the Sdf1 receptor Cxcr4 shows that both the marginal migration of PCN and the anterior migration of pontine neurons are disrupted. We further find that SDF1/CXCR4 signalling regulates these two processes cell-autonomously. As a result of disrupted neuronal migration, pontine nuclei formation was highly abnormal, with the presence of multiple ectopic pontine clusters posteriorly. The ectopic pontine clusters led to ectopic collateral branch formation from the corticospinal tract. Our results together demonstrate crucial roles for SDF1/CXCR4 in multiple aspects of PCN migration and highlight the deleterious consequence of derailed migration on proper nuclei formation. Furthermore, we provide the first in vivo evidence that pontine neurons themselves induce collateral branching from the corticospinal axons.