In vivo investigations of astrocyte-oligodendrocyte interactions

PROJECT SUMMARY Proper nervous system function depends not only on functional interactions between neurons and glia, but also between different types of glia. This proposal is focused on defining fundamental properties of interactions between two major classes of glia in the vertebrate nervous system: astrocytes and oligodendrocytes. Astrocytes are the most abundant glial cell type in the human brain and are important for central nervous system (CNS) development and function. Astrocytes are elaborate cells that extend processes that contact synapses, neurons, blood vessels, and other glial cells in the CNS. Oligodendrocytes are the myelinating glia of the CNS; they wrap axons with myelin to facilitate rapid action potential propagation and provide vital trophic support to neurons. Our long-term goals are to understand how astrocytes and oligodendrocytes functionally interact. We know that astrocytes and oligodendrocytes are connected by gap junctions and that astrocyte factors can promote myelination and remyelination. Yet the cellular and molecular bases of these interactions are incompletely understood. Our preliminary data using in vivo imaging in zebrafish demonstrate a wealth of different forms of physical interactions between astrocytes and oligodendrocytes in the developing spinal cord. This proposal will use a combination of molecular, genetic, cellular, and proteomic tools to: fully define astrocyte-oligodendrocyte myelin interactions at the cellular and molecular levels; to define novel proteins at the astrocyte-myelin interface; to understand how oligodendrocyte development and myelination are impacted when astrocyte development is altered. Our work will provide exciting new insights into how astrocyte and oligodendrocyte interactions contribute to proper nervous system function in vivo and provide a foundation for understanding the properties of these cells in human disease states.