DEVELOPMENT OF OLIGODENDROCYTES IN THE SPINAL CORD

脊髓少突胶质细胞的发育

• 批准号: 2268767
• 负责人: ROBERT H. MILLER
• 金额: $ 13.92万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2268767
• 关键词: Xenopus oocyte; blocking antibody; cell adhesion molecules; cell differentiation; cell migration; chick embryo; developmental neurobiology; electron microscopy; laboratory rat; light microscopy; myelination; nervous system transplantation; neural cell adhesion molecules; nonmammalian vertebrate embryology; oligodendroglia; spinal cord

The neuroepithelium gives rise to all the major classes of cells in the mature vertebrate CNS including neurons, astrocytes and oligodendrocytes. In most cases, the regulation of commitment of neuroepithelial cells to a specific fate and the control of precursor cell migration and differentiation is unknown. We have demonstrated that oligodendrocyte precursors in the developing rat spinal cord are initially located only in ventral regions of the spinal cord and during subsequent development migrate dorsally where they differentiate into myelin forming cells. More recently we identified a specific location in the ventral ventricular zone of the chick spinal cord in which precursors become committed to oligodendrocytes, and we described a ventral to dorsal gradient of oligodendrocyte differentiation. These observations led us to propose that the notochord, a ventrally located transient embryonic structure regulates the development of spinal cord oligodendrocytes. To determine if signals from the notochord influence the pattern of oligodendrocyte development, and whether the notochord is essential for the subsequent development of spinal cord oligodendrocytes, we will perform notochord transplantation and ablation studies in chick and Xenopus embryos. In order to myelinate CNS regions devoid of intrinsic oligodendrocyte precursors and to ameliorate pathologically demyelinated adult CNS regions, oligodendrocyte precursors must migrate considerable distances. We demonstrated that rat optic nerve oligodendrocytes were derived from progenitor cells that migrated from the brain during development, while the myelination of the complete spinal cord is dependent on the ventral to dorsal migration of oligodendrocyte precursors. Based on these studies we propose that there are-distinct pathways utilized for migration of oligodendrocyte precursors in the CNS. We have recently developed an immunolabeling paradigm which for the first time allows us to examine directly the characteristics of actively migrating oligodendrocyte precursors in vivo. Using a combination of light and electron microscopic assays, we will determine the cellular substrates of oligodendrocyte precursor migration in the intact CNS. Further, to identify the molecular mechanisms mediating oligodendrocyte precursor migration, in vivo antibody perturbation studies will be compared with the analysis of oligodendrocyte precursor migration over defined molecular substrates in vitro. These studies will provide new and important information on the regulation of oligodendrocyte development in the vertebrate CNS. Such information is essential for designing successful approaches to induce remyelination following injury or demyelinating diseases such as multiple sclerosis.

神经上皮产生了所有主要类细胞中的所有主要细胞 成熟的脊椎动物中枢神经系统，包括神经元，星形胶质细胞和少突胶质细胞。 在大多数情况下，调节神经上皮细胞对A的承诺 特定的命运和前体细胞迁移的控制和 分化是未知的。我们已经证明了少突胶质细胞 发育中的大鼠脊髓中的前体最初仅位于 脊髓的腹侧区域以及随后的发育 背侧迁移，分化为髓磷脂形成细胞。更多的 最近，我们确定了腹心室区域的特定位置 前体致力于的小鸡脊髓 少突胶质细胞，我们描述了一个腹侧至背侧梯度的 少突胶质细胞分化。这些观察结果使我们提出 Notochord，一种位于腹侧的瞬态结构，可调节 脊髓少突胶质细胞的发展。确定信号是否 从努力影响少突胶质细胞发展的模式， 以及努力是否对于随后的发展至关重要 脊髓少突胶质细胞，我们将进行诺修的移植 和小鸡和爪蟾胚胎的消融研究。 为了髓鞘CNS区域，没有固有的少突胶质细胞 前体和改善病理上脱髓鞘的成年中枢神经系统 区域，少突胶质细胞前体必须迁移相当大的距离。 我们证明了大鼠视神经少突胶质细胞是从 发育过程中从大脑迁移的祖细胞，而 完整脊髓的髓鞘形成取决于腹侧 少突胶质细胞前体的背侧迁移。基于这些研究 提出，有用于迁移的途径 中枢神经系统中的少突胶质细胞前体。我们最近开发了 免疫标记范式，这是第一次让我们检查 直接主动迁移少突胶质细胞的特征 体内前体。使用光和电子显微镜的组合 测定，我们将确定少突胶质细胞的细胞底物 完整的中枢神经系统中的前体迁移。此外，要识别分子 介导少突胶质前体迁移的机制，体内抗体 扰动研究将与少突胶质细胞的分析进行比较 前体迁移在体外定义的分子底物上。这些 研究将提供有关调节的新的重要信息 脊椎动物中心的少突胶质细胞发育。这样的信息是 设计成功的方法以诱导再生的必要 受伤或脱髓鞘疾病（例如多发性硬化症）。