The long-term goal of this research project is to gain understanding of how oligodendrocytes (and Schwann cells) myelinate axons. Realizing that none of the proteins involved in the early recognition and assembly stages of myelination were unknown, a strategy was developed to identify such proteins through isolation of complementary DNA molecules that represent messenger RNAs located at sites where myelin sheaths assemble. Studies of the developmental expression patterns of some of these mRNAs (over 80 were identified) showed that they fell into two developmental groups. One group was not strongly expressed until myelination was well under way (postnatal day 10 in rat). A second group, nearly equal in number to the first group, was expressed earlier and had higher expression in tissues with smaller myelinated fibers. With techniques used to identify these mRNAs, studies will be conducted to identify a third group of mRNAs, those expressed preferentially at times that oligodendrocyte processes first contact the axons they will myelinate. Once these mRNAs are identified, studies will be conducted to locate the sites where mRNAs and proteins are expressed in the developing nervous system to insure that the proteins are indeed important for early stages of myelination. The myelinated nervous system evolved in a common ancestor of all jawed vertebrates, including cartilaginous and teleost fishes, amphibians, reptiles, birds and mammals. This development required recruitment of proteins that allowed myelination to take place in the common ancestor. Comparative studies between rats and sharks are planned and will be used to help us understand how the myelinated nervous system originated.
