The myelin sheath is essential for normal conduction in nerves and is altered in multiple sclerosis and Guillain-Barre diseases. Understanding how myelin is formed and repaired requires basic studies of the differentiation of myelin-forming cells both in vitro and in vivo. We are now studying the precursor cells of oligodendrocytes in the developing rat CNS and the molecules that trigger their mitosis and differentiation. We have demonstrated that the minor mitogen for the O-2A progenitor cell is platelet- derived growth factor (PDGF) synthesized by Type 1 astrocytes. An immortalized rat CNS cell line has been established as a model for Type 1 astrocytes, using a retroviral vector. We have developed a method to purify O-2A progenitors (which give rise to both oligodendrocytes and Type 2 astrocytes) from the brain and studied their responses to several growth factors including PDGF and insulin-like growth factor I (IGF-I). These progenitors first proliferate in response to PDGF and then evolve in a later precursor which responds to IGF-I to generate oligodendrocytes. Using Northern blot analysis and in situ hybridization, we analyzed the expression of all myelin protein genes during myelination and dysmyelination in the rodents. In an experimental disease caused by a corona virus in mice, we are studying the mechanisms of remyelination in two ways: first we characterize the glial cells involved in myelin repair both in vivo and in vitro and second, we identify early forms of myelin basic protein transcripts in and around the lesions. Our results suggest that remyelination recapitulates the development programs of myelination.
