Unglued Glia, a Seven Transmembrane Protein Essential for Glia Differentiation

描述（由申请人提供）：该项目的目的是为理解新发现的基因unglue glia （ugg）在胶质细胞发育过程中的功能奠定基础。我们最近已经证明ugg基因对神经胶质细胞的发育至关重要，迄今为止，只有少数蛋白质被确定在指导神经胶质细胞发育中起特定作用。神经胶质细胞对神经元的支持和维持至关重要，如髓鞘轴突，使动作电位快速传播。胶质细胞还介导神经发育的许多方面，包括轴突引导、指导和介导突触功能、控制血流和大脑免疫反应1-4。研究指导神经胶质细胞发育的基因对许多疾病具有重要意义。例如，了解如何引导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目标的自身免疫性疾病。为了制定损伤后神经组织再生的策略，了解胶质细胞分化的因素是必不可少的。神经胶质干细胞也是脑癌、胶质瘤的主要来源，而特异性靶向控制神经胶质分化的基因，如ugg，代表了一种治疗基于神经胶质的癌症的有希望的方法。我们在果蝇模型动物有机体中发现了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基于胶质细胞的病理治疗的研究，如多发性硬化症和胶质瘤。

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.