EXPRESSION OF NEUROMODULIN (GAP-43) AND ITS REGULATION BY BASIC FIBROBLAST GROWTH-FACTOR DURING THE DIFFERENTIATION OF O-2A PROGENITOR CELLS

In a recent work we have shown that neuromodulin (Nm, also known as GA P-43), a protein kinase C substrate, previously believed to be express ed exclusively in neurons, is also present in glial cells. Here we inv estigated the expression of Nm and its mRNA in O-2A glial progenitor c ells (common precursor for oligodendrocytes and type-2 astrocytes) dur ing their development in secondary culture and under the influence of basic fibroblast growth factor (bFGF). The different stages of oligode ndrocyte development were characterized by the expression of surface m arkers: A2B5, which identifies 0-2A glial precursor cells, and 04 and galactocerebroside (GC), which characterize later developmental stages . The number of cells expressing Nm (about 90% at culture initiation) decreased rapidly during the first 2 days and reached a plateau at aro und 30-40%. The level of Nm mRNA followed a similar kinetic. Immunocyt ochemistry demonstrated that at 4 days in vitro about 25-30% cells wer e A2B5+, 30-40% Nm+, a high percentage (60-70%) O4+, and 35-40% GC+. N early all of the morphologically immature A2B5+ cells expressed also t he Nm antigen, very few of the O4+ cells still expressed Nm and almost no cells expressed both GC and Nm. Most O4+ cells developed a typical oligodendrocyte morphology and were essentially GC+. This study also showed that in the presence of serum, the A2B5+ Nm+ and O4+ Nm+ (GC-) cells retained their bipotentiality and differentiated into GFAP+ (gli al fibrillary acidic protein) Nm+ type-2 astrocytes. The bFGF was foun d to stimulate the proliferation of Nm+ 0-2A precursor cells and to in crease the level of Nm mRNA. At 4 days under this culture condition, t he predominant cell type was A2B5+ and Nm+. Only 25-35% of the cells w ere O4+, but 90-95% of them were Nm+. Very few GC+ cells were visible in the presence of bFGF, but 20-40% of them were Nm+. These data indic ate that Nm is essentially associated to glial 0-2A precursor cells an d further confirm that bFGF blocks the differentiation of these cells. It is suggested that Nm plays a role in the plasticity (developmental potential) of the bipotential 0-2A progenitor cells. (C) 1993 Wiley-L iss, Inc.