Investigating Glial Interactions Across the Motor Exit Point During Development

研究发育过程中运动出口点的神经胶质相互作用

• 批准号: 9094711
• 负责人: Sarah C Kucenas
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9094711
• 关键词: Ablation; Adolescent; Adult; Axon; Candidate Disease Gene; Cell Communication; Cells; Charcot-Marie-Tooth Disease; Child; Color; Coupled; Data; Defect; Degenerative Disorder; Demyelinations; Development; Diagnosis; Disease; Dorsal; Future; Genetic; Health; Image; Injury; Lead; Light; Maintenance; Mediating; Methods; Molecular; Molecular Analysis; Motor; Motor Neurons; Muscle; Muscular Atrophy; Myelin; Nerve; Nerve Degeneration; Nervous system structure; Neural Crest; Neural Crest Cell; Neural tube; Neuraxis; Neuroglia; Oligodendroglia; Organism; Peripheral; Peripheral Nervous System; Permeability; Plant Roots; Play; Population; Role; Schwann Cells; Signal Transduction; Specific qualifier value; Spinal; Spinal Cord; Spinal Ganglia; Stem cells; Structure; System; Time; Zebrafish; cell type; genetic manipulation; in vivo; information gathering; insight; migration; mutant; myelinopathy; neurogenesis; novel; prevent; screening

 DESCRIPTION (provided by applicant): Development of a functional and efficient nervous system requires the orchestrated migration and differentiation of axons and their associated glia. Motor axons connect the central nervous system (CNS) with targets in the periphery, including muscle. These axons interact with myelinating glial cells both in the CNS and peripheral nervous system (PNS). Ultimately, the differentiation of these two distinct glial populations forms a specialized structure known as the transition zone (TZ), which exists at every boundary between the spinal cord and periphery. Interestingly, at motor exit point (MEP) TZs, oligodendrocytes and peripheral myelinating glia normally stay restricted to their respective half of the nervous system, while other glia, including perineurial glia and a newly described population of cells, MEP glia, freely migrate from the spinal cord out into the periphery. How MEP TZs are selectively permeable, restricting myelinating cells from mixing, while allowing the passage of other populations, is unknown. In this project, we will characterize the development and function of a novel population of glia, motor exit point (MEP) glia, that we demonstrate are essential for restricting oligodendrocyte progenitor cells (OPC) to the spinal cord (Aim 1). In Aim 2, using both a candidate and unbiased approach, we will investigate the molecular mechanism that mediates MEP glia-OPC interactions during development. Defects in the development or maintenance of myelin along axons are the cause of many disorders collectively known as myelinopathies, one such example being Charcot-Marie-Tooth Disease (CMT). Some of the most severe types of this disease lead to demyelination, neurodegeneration and subsequent muscle atrophy in young children. Utilizing an in vivo system, zebrafish, to directly investigate the glial-glial interactions that establish MEP TZs, we will provide important insights into how functional nervous systems are assembled, maintained and behave during disease.

 描述（由申请人提供）：功能性和有效的神经系统的发育需要轴突及其相关神经胶质的协调迁移和分化。运动轴突连接中枢神经系统（CNS）与外周靶点，包括肌肉。这些轴突与CNS和外周神经系统（PNS）中的髓鞘形成胶质细胞相互作用。最终，这两种不同的神经胶质细胞群的分化形成了一种称为过渡区（TZ）的特殊结构，它存在于脊髓和外周之间的每一个边界。有趣的是，在运动出口点（MEP）TZs，少突胶质细胞和外周髓鞘神经胶质细胞通常停留在其各自的神经系统的一半，而其他胶质细胞，包括神经束膜胶质细胞和一个新描述的细胞群体，MEP胶质细胞，自由地从脊髓迁移到外周。MEP TZs如何选择性渗透，限制髓鞘形成细胞混合，同时允许其他群体通过，这是未知的。在这个项目中，我们将描述一种新的神经胶质细胞，运动出口点（MEP）神经胶质细胞，我们证明是必不可少的限制少突胶质细胞祖细胞（OPC）的脊髓（目标1）的发展和功能。在Aim中 2、采用候选和无偏的方法，我们将研究在发育过程中介导MEP胶质细胞-OPC相互作用的分子机制。髓鞘沿着轴突的发育或维持缺陷是统称为髓鞘病的许多疾病的原因，一个这样的例子是腓骨肌萎缩症（CMT）。这种疾病的一些最严重的类型导致脱髓鞘、神经变性和随后的幼儿肌肉萎缩。利用体内系统，斑马鱼，直接研究建立MEP TZs的神经胶质-神经胶质相互作用，我们将提供重要的见解功能神经系统如何组装，维护和疾病期间的行为。