Molecular mechanisms of the neuronal migration in the brain

小脑前核的神经元，包括脑桥核（PN）、外楔状核（ECN）、外侧网状核（LRN）和下橄榄核（ION），均在不同时期产生于下菱形唇（髓质背缘）。然后它们切向迁移，并最终在同侧（PN和ION）或对侧（ECN和LRN）的腹中线底板（FP）上停止其适当位置。它们迁徙的特点提出了一些问题：它们是如何切线迁移的？为什么他们中的一些人越过了FP，而另一些人没有；他们如何找到正确的位置。为了回答这些问题，我们尝试在体外重建小脑前神经元的迁移。我们采用髓质平全支架外植体培养，结合全组织表达GFP的转基因大鼠下菱形唇移植，观察在类体环境下神经元的迁移情况。培养2天后，观察到许多gfp阳性的神经元迁移到寄主外植体中。这些细胞中的大多数像在体内一样，沿着切向的路径走向FP。免疫染色也显示它们表达TAG-1和DCC。3天后，他们中的一些人越过FP继续迁移。这些神经元最初被腹中线的底板（FP）吸引。然而，在越过中线后，它们失去了对FP的反应性，并被鼻翼板（AP）吸引。这些结果表明，在小脑前神经元跨中迁移过程中，迁移细胞对有吸引力的引导信号的反应发生了关键变化。

The neurons of the precerebellar nuclei, which include the pontine nuclei (PN), the external cuneatus nucleus (ECN), the lateral reticular nucleus (LRN), and the inferior olivary nucleus (ION), are all generated from lower rhombic lips (dorsal rims of the medulla) at different periods. They then migrate tangentially and finally stop their proper positions ipsilaterally (PN and ION) or contralaterally (ECN and LRN) to the ventral midline, floor plate (FP). The features of their migrations raise some questions about how they migrate tangentially ; why do some of them cross the FP, but the others not ; how do they find their correct positions. To begin to answer these questions, we have made an attempt to reconstitute the precerebellar neuronal migration in vitro. We adopted the flat-whole mount explant culture of the medulla in combination with the transplantation of lower rhombic lip from the transgenic rat that expresses GFP in all tissues to visualize the migrating neurons in in vivo-like environment. After 2 days in culture, many GFP-positive neurons with a long leading process migrating out into the host explant were observed. Most of these cells took a tangential path toward the FP as they do in vivo. Immunostaining also showed that they express TAG-1 and DCC. After 3 days, some of them crossed the FP and continued to migrate. These neurons were initially attracted by the floor plate (FP) at the ventral midline. However, after crossing the midline, they lost their responsiveness to the FP and became attracted by the alar plate (AP). These results identify a crucial change in the response of migrating cells to attractive guidance cues during the transmedian migration of precerebellar neurons.