The development of oligodendrocytes has many of the hallmarks of other developmental paradigms. Predetermined proliferating stem cells exit their birthplace, the embryonic subventricular zone, and migrate into the brain parenchyma, where, by mechanisms not understood, they cease migration and proliferation, and begin the process of myelination, i.e., the enwrapment of neuronal axons and the correlated expression of numerous myelin-associated genes. Although advances have been made in this area of research, large gaps remain in our understanding of oligodendrocyte development, in part reflecting a scarcity of well-defined cell-surface differentiation markers. To address this concern, Dr. Gay has made twenty-six monoclonal antibodies against cell-surface molecules on mouse oligodendrocyte precursors. These monoclonal antibodies bind oligodendrocyte precursors but not fibroblasts, T cells, B cells, macrophages, or astrocytes, suggesting that most recognize molecules specific to oligodendrocyte precursors. In addition, several monoclonal antibodies distinguish subsets of oligodendrocyte precursors, suggesting heterogeneity within a lineage of cells previously considered homogeneous. The purpose of this study is to characterize these novel markers specifically to increase our understanding of oligodendrocyte development and broadly to develop a well-defined developmental system that may be applied to basic developmental questions. Specifically, Dr. Gay will determine the expression profiles and functions of some of these new oligodendrocyte markers, determine the biochemical nature of these markers, and isolate the genes that encode them.
