Establishment and Maintenance of the Spinal Cord Transition Zones

脊髓过渡区的建立和维护

• 批准号: 8810146
• 负责人: Cody J. Smith
• 金额: $ 5.42万
• 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/8810146
• 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; neuronal circuitry; 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体系结构分为单独的域，外周神经系统（PNS）和中枢神经系统（CNS），这些轴突通过轴突连接，这些轴突通过这些域的边界传播并创建了控制脊椎动物的信息流动的方向流。尽管沿轴突沿轴突的动作电位可以自由地通过CNS/PNS边界，但对于轴突正确功能至关重要的胶质细胞不允许横向该边界。这种限制将神经系统的两个髓神经胶质亚型划分，少突胶质细胞仅限于中枢神经系统，而schwann细胞仅限于PNS。在轴突自由导航或将这些细胞与特定域分离到特定域的功能意义时，如何允许某些细胞类型横向边界。这一边界的重要性强调了，发现异位置的细胞已在包括多发性硬化症在内的多种神经系统疾病中可视化。为了使我们了解如何建立和维护该边界以产生功能性神经元电路，我们必须以使我们能够可视化边界细胞的动态相互作用的方式评估其开发。因此，我选择使用一个模型系统，该系统使我能够在完整动物中对单个细胞的特定操纵之前，之中和之后可视化细胞 - 细胞相互作用。该提议的长期目标是了解中枢神经系统和PN之间边界的发展。来自该系统的初步数据表明，源自中枢神经系统的先前未识别的细胞类型，通过中枢神经系统/PNS边界迁移，其中运动轴突退出脊髓并占据PNS，并限制了CNS位于CNS的Glia退出脊髓。同一相互作用是否还可以控制脊髓中其他CNS/PNS边界区域，将通过以下研究进一步研究：1。表征哪些胶质细胞类型位于PNS/PNS边界的PNS/PNS边界中，PNS感觉轴突传播到脊髓中。延时成像以及神经胶质细胞前体的药理学/遗传消融将使对边界神经胶质细胞的起源及其在发育过程中的细胞动力学有详细的了解。 2。研究边界建立期间神经胶质细胞的细胞 - 细胞相互作用及其在此过程中去除的结果。 3。揭示了丛/信号素信号传导的分子需求，以建立和维持神经胶质边界。