Role of neuronal migration for the formation of neuronal connections

苔藓纤维突出的小脑前神经元（PCN）的发育是切向神经元迁移的经典例子。在 PCN 中，脑桥神经元遵循刻板的前腹侧定向通路在脑桥中形成脑桥核。决定 PCN 边缘迁移和脑桥神经元前部迁移的引导机制尚不清楚。在这里，我们报道了源自脑膜组织的趋化因子 SDF1 调节 PCN 的迁移途径。 PCN 受到脑膜组织的化学吸引，这种效应与 SDF1 来源相似。对 Sdf1 受体 Cxcr4 敲除小鼠的分析表明，PCN 的边缘迁移和脑桥神经元的前部迁移均被破坏。我们进一步发现 SDF1/CXCR4 信号传导细胞自主地调节这两个过程。由于神经元迁移中断，脑桥核形成高度异常，后部存在多个异位脑桥簇。异位脑桥簇导致皮质脊髓束形成异位侧支。我们的结果共同证明了 SDF1/CXCR4 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，我们提供了第一个体内证据，证明脑桥神经元本身诱导皮质脊髓轴突的侧支分支。

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.