Establishment and Maintenance of the Spinal Cord Transition Zones

脊髓过渡区的建立和维护

• 批准号: 8718497
• 负责人: Cody J. Smith
• 金额: $ 5.15万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8718497
• 关键词: Ablation; Action Potentials; Animals; Architecture; Attention; Axon; Biological Models; Cell Communication; Cells; Coupled; Data; Development; DsRed; Excision; Figs - dietary; Genetic; Goals; Gray unit of radiation dose; Image; Information Systems; Label; Larva; Lasers; Lead; Left; Maintenance; Mediating; Modeling; Molecular; Motor; Multiple Sclerosis; Nervous System Part; Nervous System Physiology; Nervous system structure; Neural Crest; Neuraxis; Neuroglia; Neurons; Neuropathy; Oligodendroglia; Pattern; Peripheral; Peripheral Nervous System; Plant Roots; Population; Positioning Attribute; Process; Role; Schwann Cells; Semaphorins; Sensory; Signal Transduction; Spinal Cord; Testing; Time; Transgenic Organisms; Travel; Zebrafish; base; cell motility; cell type; in vivo; in vivo imaging; migration; mutant; nervous system disorder; neural circuit; neuronal cell body; plexin; precursor cell; progenitor; public health relevance; research study; spinal nerve posterior root; time use

DESCRIPTION (provided by applicant): The basic architecture of the vertebrate nervous system is divided into separate domains, the peripheral nervous system (PNS) and the central nervous system (CNS), that are connected by axons that travel through the boundary of these domains and creates a directional flow of information that controls the vertebrate body. Although the action potentials along axons that carry this information freely pass the CNS/PNS boundary, glial cells, which are essential for proper function of the axons, are not permitted to transverse this boundary. This restriction demarcates the two myelinating glial subtypes of the nervous system, with oligodendrocytes restricted to the CNS and Schwann cells limited to the PNS. How certain cell types are permitted to transverse the boundary while axons freely navigate across or the functional significance of separating these cells to specific domains is unknown. The importance of this boundary is underscored by the discovery that ectopically-located cells have been visualized in multiple neurological diseases including multiple sclerosis. In order for us to understand how this boundary is established and maintained to produce a functional neuronal circuit, we must evaluate its development in a way that allows us to visualize the dynamic interaction of the cells at the boundary. For this reason, I chose to utilize a model system that allows me to visualize cell-cell interactions before, during and after specific manipulation of single cells in an intact animal. The long-term goal of this proposal is to understand the development of the boundary between the CNS and PNS. Preliminary data from this system suggests that a previously unidentified cell-type that originates from the CNS, migrates through the CNS/PNS boundary where motor axons exit the spinal cord and occupies the PNS where it restricts CNS-located glia from exiting the spinal cord. Whether this same interaction also controls at the other CNS/PNS boundary region in the spinal cord will be further investigated by: 1. Characterizing which glial cell-types are located in the PNS and CNS at the CNS/PNS boundary that is located where PNS sensory axons travel into the spinal cord. Time-lapse imaging, and pharmacological/genetic ablation of glial cell precursors will give a detailed understanding of the origin of boundary glial cells and their cellular dynamics during development. 2. Investigating the cell-cell interactions of glial cells during boundary establishment and the consequence of their removal during this process. 3. Revealing the molecular requirement of Plexin/Semaphorin signaling for establishing and maintaining the glial boundary.

描述（由申请人提供）：脊椎动物神经系统的基本架构分为不同的域，即周围神经系统（PNS）和中枢神经系统（CNS），它们通过穿过这些域边界的轴突连接并创建控制脊椎动物身体的定向信息流。尽管携带此信息的沿轴突的动作电位自由地通过 CNS/PNS 边界，但对于轴突正常功能至关重要的神经胶质细胞不允许穿过此边界。这种限制划分了神经系统的两种髓鞘神经胶质亚型，少突胶质细胞仅限于中枢神经系统，施万细胞仅限于三七总神经系统。如何允许某些细胞类型穿越边界，同时轴突自由导航，或者将这些细胞分离到特定区域的功能意义尚不清楚。在包括多发性硬化症在内的多种神经系统疾病中观察到异位细胞的发现强调了这一边界的重要性。为了让我们了解这个边界是如何建立和维持以产生功能性神经元回路的，我们必须以一种能够使我们可视化边界处细胞的动态相互作用的方式评估其发展。出于这个原因，我选择利用一个模型系统，使我能够在对完整动物的单细胞进行特定操作之前、期间和之后可视化细胞间的相互作用。该提案的长期目标是了解 CNS 和 PNS 之间边界的发展。来自该系统的初步数据表明，一种先前未识别的源自中枢神经系统的细胞类型，通过运动轴突离开脊髓的中枢神经系统/PNS边界迁移并占据PNS，限制位于中枢神经系统的神经胶质细胞离开脊髓。这种相同的相互作用是否也控制在脊髓中的其他 CNS/PNS 边界区域将通过以下方式进一步研究： 1. 表征哪些神经胶质细胞类型位于 PNS 和 CNS 位于 PNS 的 CNS/PNS 边界处感觉轴突进入脊髓。延时成像和神经胶质细胞前体的药理学/遗传消融将详细了解边界神经胶质细胞的起源及其发育过程中的细胞动力学。 2. 研究边界建立过程中神经胶质细胞的细胞间相互作用以及在此过程中去除边界的后果。 3.揭示Plexin/Semaphorin信号传导建立和维持神经胶质边界的分子要求。