AXON GUIDANCE IN THE SPINAL CORD

这项工作的目标是确定细胞和分子事件 这是发育中的中枢神经系统中轴突引导的基础。的 最早的连合轴突轨迹的发展， 胚胎大鼠脊髓提供了一种可接近的模型系统，其中 来研究引导中枢神经系统轴突投射的线索。联合轴突 最初从背中线周向突出， 靠近脊髓的外侧边缘这个轴突的路径 迁移可能受到来自背中线的信号的调节 结构，屋顶板，并由一个 细胞外基质成分，层粘连蛋白-硫酸乙酰肝素 蛋白多糖复合物连合轴突延伸并穿过 腹中线，但突然改变其延伸方向， 旋转90度以纵向和喙状突出 在腹索内轴突转向与 一组细胞的对侧边界，称为地板 板，那横跨腹侧中线。这种转向在胚胎中被破坏 其中没有底板，这表明导航 信息与底板本身相关联。但在 除了底板细胞及其下面的基底层外， 其他潜在的引导线索的来源是： 对侧和底板外侧的神经上皮。的 在吻侧方向上引导纵向生长的线索可以是 位于脊髓内或可能源自脊髓上 源头已经建立了脊髓的体外制备物， 允许连合的可视化和实验扰动 预测随着发展。异位先露和选择性消融 不同的细胞类型和抗体干扰细胞表面 分子将被用来检查是否屋顶板调节 周向生长的方向，哪些细胞接触 在中线处需要连合生长锥进行寻路 以及这些细胞类型的功能是否由以下任何一种介导： 几种已鉴定的分子这些实验将提供 关于共同塑造轴突的线索范围的信息 投射和轴突引导中的中间靶点的作用。 尽管CNS中投射路径的普遍性和重要性 目前还没有关于可能导致 首先，引导纵向增长。实验 因此，上述内容对我们的 了解整个过程中投射路径的发展 CNS。

The goal of this work is to determine the cellular and molecular events that underlie the guidance of axons within the developing CNS. The development of the earliest commissural axon trajectory in the embryonic rat spinal cord provides an accessible model system in which to study the cues that guide CNS axonal projections. Commissural axons initially project circumferentially, away from the dorsal midline and close to the lateral edge of the spinal cord. The path of this axonal migration may be regulated by signals from the dorsal midline structure, the roof plate, and constrained laterally by an extracellular matrix component, the laminin-heparan sulphate proteoglycan complex. Commissural axons extend towards and across the ventral midline but then abruptly change their direction of extension, turning through 90 degrees to project longitudinally and rostrally within the ventral funiculus. The axonal turn occurs coincident with the contralateral boundary of a group of cells, known as the floor plate, that spans the ventral midline. The turn is disrupted in embryos in which the floor plate is absent, suggesting that navigational information is associated with the floor plate itself. However, in addition to floor plate cells and their underlying basal lamina, two other potential sources of guidance cues are: axons crossing from the contralateral side and neuroepithelium lateral to the floor plate. The cue that directs longitudinal growth in a rostral direction may be localized within the spinal cord or may emanate from a supraspinal source. In vitro preparations of spinal cord have been established that permit visualization and experimental perturbation of the commissural projection as it develops. Ectopic presentation and selective ablation of distinct cell types and antibody perturbation of cell surface molecules will be used to examine whether the roof plate regulates the direction of circumferential growth, which of the cells contacted by commissural growth cones are required for pathfinding at the midline and whether the functions of these cell types are mediated by any of several identified molecules. These experiments will provide information about the range of cues that together shape an axonal projection and the role of intermediate targets in axon guidance. Despite the prevalence and importance of projection paths in the CNS there is currently no information on the cues that are likely to operate initially to direct longitudinal growth. The experiments described above therefore have important implications for our understanding of the development of projection pathways throughout the CNS.