Platelet-derived growth factor and basic fibroblast growth factor regulatecell proliferation and the expression of notch-1 receptor in a new oligodendrocyte cell line

We generated a new cell line, N38, by conditionally immortalizing mouse oli godendrocytes (OLs) at early stages of maturation. The morphology and marke r expression pattern suggest N38 cells are similar to immature OLs. N38 cel ls were sensitive to changes in serum concentrations, and forcing the cells to differentiate in low serum at 39 degreesC significantly decreased the s urvival of the cells. Importantly, addition of PDGFaa, bFGF or astrocyte-co nditioned medium had protective effects on the cells, by increasing cell pr oliferation but not cell differentiation. This effect was receptor-mediated , Exposure of N38 cells to differentiating signals such as retinoic acid di d not cause further differentiation of the cells. The N38 cell line express es the vertebrate homolog of the Drosophila notch-1 receptor, a molecule th at appears to regulate OL differentiation. Notch-1 receptor was homogeneous ly distributed in the somas of N38 cells. Incubation of N38 cells with eith er PDGFaa or bFGF, however, induced a polarized distribution of the recepto r in the majority of the cells as well as an upregulation of receptor prote in levels. The upregulation of molecules, such the notch-1 receptor, in pat hways that control differentiation might be an important mechanism for keep ing OL precursors in an undifferentiated state during their exit of the ger minal layer and migration in the developing central nervous system. This OL cell line might constitute a suitable model for studies of regulatory mech anisms at this stage of OL differentiation. J. Neurosci. Res. 62: 319-328, 2000. (C) 2000 Wiley-Liss, Inc.