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Expression of neuromodulin (GAP‐43) and its regulation by basic fibroblast growth factor during the differentiation of O‐2A progenitor cells
Author(s) -
Deloulme J. C.,
Laeng P.,
Janet T.,
Sensenbrenner M.,
Baudier J.
Publication year - 1993
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490360205
Subject(s) - basic fibroblast growth factor , immunocytochemistry , oligodendrocyte , glial fibrillary acidic protein , galactocerebroside , progenitor cell , microbiology and biotechnology , cell culture , biology , neuroglia , growth factor , cellular differentiation , chemistry , stem cell , immunology , biochemistry , endocrinology , receptor , immunohistochemistry , myelin , central nervous system , genetics , gene
In a recent work we have shown that neuromodulin (Nm, also known as GAP‐43), a protein kinase C substrate, previously believed to be expressed exclusively in neurons, is also present in glial cells. Here we investigated the expression of Nm and its mRNA in O‐2A glial progenitor cells (common precursor for oligodendrocytes and type‐2 astrocytes) during their development in secondary culture and under the influence of basic fibroblast growth factor (bFGF). The different stages of oligodendrocyte development were characterized by the expression of surface markers: A2B5, which identifies O‐2A glial precursor cells, and O4 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 around 30–40%. The level of Nm mRNA followed a similar kinetic. Immunocytochemistry demonstrated that at 4 days in vitro about 25–30% cells were A2B5, + , 30–40% Nm + , a high percentage (60–70%)O4 + , and 35–40% GC + . Nearly all of the morphologically immature A2B5 + cells expressed also the 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 04 + Nm + (GC − )xs cells retained their bipotentiality and differentiated into GFAP + (glial fibrillary acidic protein) Nm + type‐2 astrocytes. The bFGF was found to stimulate the proliferation of Nm + 0–2A precursor cells and to increase the level of Nm mRNA. At 4 days under this culture condition the predominant cell type was A2B5 + and Nm + . Only 25–35% of the cells were 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 indicate that Nm is essentially associated to glial O‐2A precursor cells and 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. © 1993 Wiley‐Liss, Inc.