Important advances in neuroscience research are currently being made through application of molecular biological techniques. Use of molecular probes is providing new insight into brain development, brain function and a number of pathological conditions. The current studies are designed to elucidate the regulation of myelination in the central nervous system through use of molecular probes. Myelination is a crucial event for normal brain development and demyelinating diseases such as multiple sclerosis seriously affect neurological function. Because of the complexity of brain development, investigation of the regulation of oligodendrocyte differentiation and myelin formation has been difficult. Isolation and utilization of molecular probes for oligodendrocyte differentiation provides a new approach to the study of CNS myelination. In the current studies, clones of the cDNAs for the myelin proteolipid and basic proteins will be isolated, sequenced and characterized. These clones and genomic clones, isolated by screening genomic libraries with the cDNA clones, will be used to assess the control of the expression of these myelin proteins. In further studies on the regulation of oligodendrocyte differentiation and myelination, we will isolate previously undescribed cDNA clones which may function in oligodendrocyte differentiation. A cDNA library will be produced which will be highly enriched in oligodendrocyte cDNAs. Selected clones from this library will be sequenced and characterized to identify previously unknown oligodendrocyte genes. The expression of the different oligodendrocyte genes will be investigated in several experimental systems, e.g., a neurological mutant mouse strain which has altered myelination and, more extensively, a primary brain cell culture system which can be experimentally manipulated to induce differentiation of oligodendrocytes and to reduce differentiation of astrocytes. Investigation of oligodendrocyte differentiation and the regulation of expression of the proteolipid and basic protein genes as well as these other oligodendrocyte genes may have great significance for future studies on remyelination in the central nervous system, with particular reference to multiple sclerosis.
