| These studies were undertaken to investigate differences in oligodendrogenesis between gray matter (GM) and white matter (WM) of the brain. We first identified differences in normal oligodendrogenesis between GM and WM, noting that compared to WM, GM oligodendrogenesis was slower and occurred in a subcortical WM to pial surface gradient. The dysmyelinating mutant Jimpy also exhibited GM/WM differences in oligodendrocyte production. Jimpy WM exhibited protracted oligodendrocyte production, whereas jimpy cerebral cortex had decreased oligodendrocyte production. These studies suggest a differential response by GM and WM to the PLP/DM20 mutation. To delineate specific mechanisms responsible for GM/WM differences in oligodendrogenesis, we contrasted GM and WM oligodendrocyte development in a cell culture system. Although the jp/msd study suggested the possibility of intrinsic differences between oligodendrocyte progenitor cells (OPCs), our in vitro studies found no evidence of either intrinsic differences between GM and WM OPCs or differences between GM and WM environments. In addition, the presence of numerous OPCs in the prenatal cerebral cortex suggests OPC migration is not a limiting factor delaying oligodendrogenesis in GM.;Also present in both GM and WM mixed cultures was a large population of NG2+/A2B5- cells that failed to differentiate into oligodendrocytes. Thus, these NG2+/A2B5- cells are reminiscent of the in vivo NG2+ cells that fail to differentiate ("adult" NG2+ cells). Three experiments were conducted to address the question of whether NG2+/A2B5- cells are members of the oligodendrocyte lineage. The results of these studies provide strong evidence that NG2+/A2B5- cells cannot directly differentiate into oligodendrocytes; however, NG2+/A2B5- cells do produce A2B5+ OPCs. Thus, during early postnatal development, all CNS NG2+ cells belong to the oligodendrocyte lineage, and the vast majority (93%) of these cells is capable of generating OPCs. Purified NG2+/A2B5- cells generated equivalent numbers of OPCs and NG2+/A2B5- cells, suggesting an asymmetric division generated the two cell types. That OPCs were not generated at the expense of NG2+/A2B5- cells provides further evidence that the NG2+/A2B5- cell or "adult" NG2+ cell is a distinct glial cell type in the CNS and not merely an OPC that has failed to differentiate. |
