Myelin-forming cells enwrap axons to allow fast conduction along major nerve tracts. In multiple sclerosis (MS) and some CNS viral diseases, damage to myelin~forming cells result in important neurological dysfunction. Our studies on developing rat oligodendrocytes have shown that platelet~derived and basic fibroblast growth factors (PDGF and bFGF) trigger migration and mitosis of oligodendrocyte progenitors (OP). During differentiation, oligodendrocytes express transforming growth factor (TGF)~beta 1, 2 and 3 isoforms and secrete an inhibitor of cell mitosis that can be neutralized with antibodies to TGF beta. Thus, TGF~beta produced by differentiating cells may limit growth and promote oligodendrocyte differentiation in an autocrine manner. To further our understanding of oligodendrocyte differentiation signals, we characterize the myelinating properties of a rat OP cell line. These cells were "tagged" with the Lac Z gene and grafted into the spinal cord of dysmyelinated rats where they myelinated up to 7 mm of the dorsal tracts. Another gene tag (MX) has been used to follow the migration of grafted cells, which appear to be attracted toward a demyelinating lesion in mice. Our studies of the human oligodendrocyte lineage demonstrate that the human myelinated brain contains a discrete subpopulation of glial cells expressing two oligodendrocyte~specific and developmentally regulated genes, the PDGF receptor alpha and the Myelin Transcription Factor I (MyTI). In addition, a substantial proportion of glial cells of the adult human white matter express the early forms of myelin basic protein (MBP) transcripts which are characteristic of the premyelinating stage. These genes are also expressed in cultured human oligodendrocytes and~or their precursor cells. Contrary to what happens with adult rat OP, bFGF and PDGF fail to stimulate human OP to divide. However, bFGF induces human oligodendrocytes to rapidly regenerate their processes in vitro and to dedifferentiate into OP expressing MyTI and early MBP transcripts. Thus, phenotypic plasticity rather than mitogenic potential may account for the regeneration of myelin~forming cells in the adult human brain.
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NIH ExPorter