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Regulation of Glial Cell Size

神经胶质细胞大小的调节

基本信息

批准号：
9474231
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
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2019-06-30
项目状态：
已结题

项目摘要

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（由申请方提供）：在器官发育过程中缩放组织层的大小。在神经系统中，神经元和神经胶质的大小必须协调，特别是对于神经胶质，例如与轴突或神经元细胞体紧密相关的施万细胞和卫星细胞。雪旺细胞和卫星神经胶质细胞对神经损伤的不适当生长与慢性疼痛有关。尽管它很重要，关于神经元和神经胶质细胞的生长是如何协调的还知之甚少。在果蝇中，至少有两种类型的神经胶质细胞通过增加DNA含量（倍性）来增加细胞大小，这是整个植物和动物王国产生大细胞的通用策略。通过测量倍性来监测神经胶质细胞大小和通过改变倍性来改变神经胶质细胞生长的能力为果蝇中用于分析神经系统发育的强大工具包提供了额外的实验优势。我们建议利用倍性在果蝇神经系统中的胶质细胞生长，以确定机制，协调神经胶质细胞和神经元之间的发展。我们将研究一种类型的表面胶质细胞，神经束膜下胶质细胞（SPG），提供血脑屏障。SPG通过增加倍性而不是分裂来生长以容纳下面的神经元团，同时保留血脑屏障的完整包膜。SPG倍性受神经元质量控制。在周围神经系统中，包裹神经胶质（WG）包裹轴突。它们的大小增加到50倍而不分裂，显然是通过增加倍性。我们将明确WG多倍体化的作用和调控。我们的具体目标测试三个假设：1）神经元质量通过增加神经元活性和/或机械张力促进SPG的倍性和大小增加; 2）WG的倍性增加对于生长是必要的，以允许伸长轴突的鞘化;和3）外周神经中三个胶质层的大小是协调的。此外，我们将定义在正常条件下的SPG和WG的转录组，当生长被相邻的组织层修改，作为一种手段来识别基因，指定这些神经胶质细胞的功能，并改变倍性，以响应来自其他细胞的线索。该提案的目标将通过使用果蝇遗传工具来标记细胞，抑制基因活性或过度表达具有精致发育特异性的基因来实现。