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内轴突指导的基础。这个 中国最早的连合轴突轨迹的发育 胚胎大鼠脊髓提供了一个可访问的模型系统，在其中 研究指导中枢神经系统轴突投射的线索。连合轴突 最初沿圆周方向突出，远离背中线 靠近脊髓侧缘的。这个轴突的路径 迁移可能受来自背中线的信号的调节 结构、屋顶板，并由 细胞外基质成分，层粘连蛋白-硫酸乙酰肝素 蛋白多糖复合体。连合轴突伸向并横跨 腹中线，然后突然改变它们的伸展方向， 旋转90度，以纵向和纵向投影 在腹索内。轴突转折的发生与 一组单元格的对侧边界，称为底边 板块，横跨腹侧中线。这一转变在胚胎中被打破了 其中没有底板，这表明导航 信息与地板本身相关。但是，在 除底板细胞及其下面的基底膜外，还有两个 其他潜在的引导线索来源包括：从 对侧和底板外侧的神经上皮细胞。这个 引导纵向生长的线索可能是 位于脊髓内或可能发自脊柱上 消息来源。脊髓的体外制剂已被证实 允许对连合进行可视化和实验微扰 随着它的发展而投射。异位介绍和选择性消融 不同的细胞类型和细胞表面的抗体扰动 分子将被用来检查屋顶板是否调节 周向生长方向，哪些细胞与 在中线寻找路径需要连合生长锥体 以及这些细胞类型的功能是否由任何一种 几个已确认的分子。这些实验将提供 有关共同形成轴突的线索范围的信息 投射和中间靶在轴突引导中的作用。 尽管投射路径在中枢神经系统中的普遍存在和重要性 目前还没有关于可能会 最初的操作是引导纵向增长。这些实验 因此，上述内容对我们的 对投射通路在整个大脑中的发展的理解 中枢神经系统。

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.