Regulation of Glial Cell Size

神经胶质细胞大小的调节

• 批准号: 8942144
• 负责人: Terry L. ORR-WEAVER
• 金额: $ 42.66万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8942144
• 关键词: Affect; Animals; Axon; Blood - brain barrier anatomy; Cell Size; Cells; Coupled; Cues; Development; Drosophila genus; Failure; Gene Expression Profile; Genes; Genetic; Goals; Growth; Label; Length; Link; Measures; Mechanics; Modeling; Molecular; Monitor; Nerve; Nervous system structure; Neuraxis; Neuroglia; Neurons; Peripheral Nerves; Peripheral Nervous System; Plants; Ploidies; Polyploidy; Regulation; Regulatory Pathway; Role; Schwann Cells; Signal Pathway; Specific qualifier value; Specificity; Supporting Cell; Surface; Testing; Tissues; cell growth; cell type; chronic pain; insight; nervous system development; neuronal cell body; neuronal growth; organ growth; overexpression; public health relevance; relating to nervous system; response; satellite cell; tool; tumor

 DESCRIPTION (provided by applicant): The size of tissue layers is scaled during the development of organs. In the nervous system, the size of neurons and glia must be coordinated, particularly for glia such as Schwann cells and satellite cells that are in tight association with axons or neuronal cell bodies. Inappropriate growth of Schwann cells and satellite glia cells in response to nerve damage is linked to chronic pain. Despite its importance, little is understood about how neuronal and glial growth are coordinated. In Drosophila, at least two types of glia increase cell size by increasing DNA content (ploidy), a universal strategy to produce large cells throughout the plant and animal kingdoms. The ability to monitor glial cell size by measuring ploidy and to alter glial cell growth by changing ploidy provides additional experimental advantages to the powerful toolkit in Drosophila for analysis of development of the nervous system. We propose to exploit glial growth by ploidy in the Drosophila nervous system to define mechanisms that coordinate growth between glia and neurons in development. We will investigate one type of surface glia, the subperineurial glia (SPG), that provide the blood-brain barrier. SPG grow to accommodate the underlying neuronal mass while retaining an intact envelope for the blood-brain barrier by increasing ploidy rather than dividing. SPG ploidy is controlled by neuronal mass. The wrapping glia (WG) ensheath axons in the peripheral nervous system. They increase up to 50 fold in size without dividing, apparently by increasing ploidy. We will define the role and regulation of polyploidization of WG. Our specific aims test three hypotheses: 1) neuronal mass promotes ploidy and size increases for the SPG by increased neuronal activity and/or mechanical tension; 2) increased ploidy of the WG is necessary for growth to permit ensheathment of elongating axons; and 3) the size of the three glial layers in the peripheral nerves is coordinated. Additionally, we will define the transcriptomes of the SPG and WG under normal conditions and when growth is modified by adjacent tissue layers, as a means to identify genes that specify functions of these glia and alter ploidy in response to cues from other cells. The goals of this proposal will be achieved by using Drosophila genetic tools to label cells, inhibit gene activity, or overexpress genes with exquisite developmental specificity.

 描述（由适用提供）：组织层的大小在器官的发展过程中进行缩放。在神经系统中，必须协调神经元和神经胶质的大小，特别是对于与轴突或神经元细胞体密切相关的雪兰细胞和卫星细胞等神经胶质。雪旺细胞和卫星胶质细胞对神经损伤的不当生长与慢性疼痛有关。尽管很重要 关于神经元和神经胶质生长的协调方式知之甚少。在果蝇中，至少两种类型的神经胶质通过增加DNA含量（倍粒）来增加细胞的大小，这是一种在整个动植物王国中产生大细胞的普遍策略。通过测量倍性和通过变化来改变神经胶质细胞生长的能力，可以为果蝇中强大的工具包提供其他实验优势，以分析神经系统的发展。我们建议探索果蝇神经系统中酶的神经胶质生长，以定义与发育中神经胶质和神经元之间生长的机制。我们将研究一种提供血脑屏障的一种表面胶质细胞胶质细胞胶质细胞胶质神经胶质细胞（SPG）。 SPG生长以适应潜在的神经元肿块，同时通过增加倍倍而不是分裂来保留血脑屏障的完整包膜。 SPG倍性受神经元质量控制。包裹神经胶质（WG）的外周神经系统中的轴突。它们的大小最多增加了50倍，而无需分裂，显然是通过增加倍倍。我们将定义WG多倍体的作用和调节。我们的具体目的测试了三个假设：1）神经元质量通过增加的神经元活性和/或机械张力来促进SPG的倍数增加； 2）WG的倍增性增加对于允许伸长轴突的启动是必要的； 3）外周神经系统中三个神经胶质层的大小是协调的。此外，我们将在正常条件下定义SPG和WG的转录组，以及当相邻组织层修饰生长时，作为识别指定这些神经胶质功能的基因并响应其他细胞提示的基因。该提案的目标将通过使用果蝇遗传工具来标记细胞，抑制基因活性或具有独特发育特异性的过表达基因。