Unglued Glia, a Seven Transmembrane Protein Essential for Glia Differentiation

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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.