Unglued Glia, a Seven Transmembrane Protein Essential for Glia Differentiation

描述(申请人提供)：该项目的目标是为了解新发现的基因脱胶胶质细胞(UGG)在神经胶质细胞发育过程中的功能奠定基础。我们最近发现，UgG基因对胶质细胞的发育是必不可少的，到目前为止，只有少数几种蛋白质被鉴定出来，它们在指导神经胶质细胞的发育中发挥着特定的作用。神经胶质细胞对神经元的支持和维持是必不可少的，例如，使轴突分化以允许动作电位的快速传播。神经胶质细胞还参与神经发育的许多方面，包括轴突引导、指导和调节突触功能、控制血液流动和大脑1-4的免疫反应。对指导胶质细胞发育的基因的研究在许多疾病中都有重要的意义。例如，了解如何指导神经胶质细胞的分化对于开发治疗多发性硬化症的方法至关重要，多发性硬化症是一种以胶质细胞为靶点的自身免疫性疾病。为了开发损伤后再生神经组织的策略，了解分化胶质细胞的因素是必不可少的。胶质干细胞也是脑癌和胶质瘤的主要来源，针对控制神经胶质分化的基因，如uGG，是治疗神经胶质癌的一种有前途的方法。我们在果蝇模式动物有机体果蝇中发现了UGG，我们将继续使用果蝇系统来表征这种新蛋白质在指导神经胶质细胞命运中的作用。我们预测，脊椎动物版本的ugg将在人类胶质细胞的分化过程中发挥同样重要的作用，这里提出的研究将有助于指导未来治疗多发性硬化症和胶质瘤等基于胶质细胞的疾病的研究。 公共卫生相关性：该项目的目标是为了解膜蛋白的功能奠定基础，该蛋白是我们最近发现的对神经胶质细胞分化至关重要的蛋白。神经胶质细胞发育在损伤后神经组织再生中起重要作用，在这一过程中可能有潜在的治疗作用。UGG也可能被证明是治疗以胶质细胞为基础的病理疾病的可行靶点，如多发性硬化症和脑癌的主要来源，胶质瘤。

DESCRIPTION (provided by applicant): The objective of this project is to lay the groundwork towards understanding the function of the newly discovered gene unglued glia (ugg), during glial cell development. We have recently shown that the ugg gene is essential for the development of glial cells and only a handful of proteins have been identified to date that play a specific role in directing glial cell development. Glial cells are essential for the support and maintenance of neurons, such as mylenating axons to allow rapid propagation of action potentials. Glia also mediate many aspects of neural development including axon guidance, directing and mediating synapse function, controlling blood flow, and immune responses in the brain 1-4. The study of the genes that direct glia development has important implications in many diseases. For example, understanding how to direct the differentiation of glia is essential in developing approaches for the treatment of Multiple Sclerosis, an autoimmune disease that targets glia. For developing strategies to regenerate nervous tissue after an injury an understanding of the factors that differentiate glia is essential. Glia stem cells are also the major source of brain cancers, gliomas, and specifically targeting genes that control glial differentiation, such as ugg, represents a promising approach in treating glial based cancers. Our discovery of ugg was made in the fruit fly model animal organism, Drosophila and we will continue to use the Drosophila system to characterize this new protein's role in directing glial cell fates. We predict that the vertebrate version of ugg will have an equally important role in the differentiation of human glia and the studies proposed here will help guide future research for the treatment of glial cell based pathologies such as Multiple Sclerosis and gliomas. PUBLIC HEALTH RELEVANCE: The objective of this project is to lay the groundwork towards understanding the function of the membrane protein, ugg, that we recently discovered to be essential for glia cell differentiation. Glial cell development has an important role in regenerating nervous tissue after an injury and ugg could have potential therapeutic use in this process. Ugg may also prove to be a viable target for the treatment of glial cell based pathologies such as Multiple Sclerosis and the major source of brain cancers, gliomas.