Down‐regulation of GAP‐43 During Oligodendrocyte Development and Lack of Expression by Astrocytes In Vivo: Implications for Macroglial Differentiation

Abstract

The discovery of molecular markers which are selectively expressed during the development of specific classes of rat central nervous system macroglia has greatly advanced our understanding of how these cells are related. In particular, it has been shown in tissue culture that oligodendrocytes and some astrocytes (type-2) may be derived from a common progenitor cell (O-2A progenitor). However, the existence of type-2 astrocytes in vivo has yet to be unequivocally established. Recently, it has been reported that the neural-specific growth-associated protein-43 (GAP-43, otherwise known as B-50, F1, pp46 and neuromodulin) may be expressed by cells of the O-2A lineage in vitro. We set out to examine the cellular specificity of GAP-43 in O-2A progenitors and their descendants in vitro and in vivo. Using a polyclonal antiserum against a GAP-43 fusion protein we have shown the presence of immunoreactive GAP-43 in the membranes of bipotential O-2A glial progenitor cells and type-2 astrocytes by Western blotting and immunocytochemistry of cells in culture. In contrast to previous studies, double labelling with mature oligodendrocyte markers showed that GAP-43 is down-regulated during oligodendrocyte differentiation in vitro. Immunohistochemical staining of sections of developing rat brain demonstrated the same developmental regulation of GAP-43, suggesting that oligodendrocytes only express GAP-43 at immature stages. In addition, normal and reactive astrocytes in tissue sections were not labelled with GAP-43.

Identifying the Cellular Targets of Drug Action in the Central Nervous System Following Corticosteroid Therapy

“…APOE has a major role in lipid metabolism, 39 but its role in the genesis of lipid rich myelin sheaths in the CNS is currently unclear. Gap43 is expressed in immature oligodendrocytes but down regulated during maturation; 40 although we did not detect morphological alterations in CS treated oligodendrocytes, we cannot currently rule out alterations in their engagement with axons.…”

Expression of the immunoglobulin superfamily cell adhesion molecule F3 by oligodendrocyte-lineage cells

“…The Ig superfamily member L1, which was originally described on neurons and Schwann cells (Rathjen and Schachner, 1984;Faissner et al, 1984), has also been ascribed to glial cells, albeit with amino acid modifications (Takeda et al, 1996). The growthassociated protein 43 (GAP-43) was originally thought to be exclusive to neurons, whereas it was later observed to be additionally expressed by immature oligodendrocytes (Curtis et al, 1991) and downregulated upon oligodendrocyte differentiation (Deloulme et al, 1990(Deloulme et al, , 1993. The oligodendrocyte myelin glycoprotein (OMgp) was named after its seemingly exclusive distribution in the myelin sheath (Mikol et al, 1990), the expression was later also extended to subpopulations of neurons.…”

Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation

“…GAP43, a growth and regeneration-associated marker of process extension, was enriched more than fourfold in WMPCs, confirming earlier reports of the expression of GAP43 by rodent oligodendrocyte progenitors. 15 GAD67 mRNA, which encodes glutamate decarboxylase and as such serves as a marker of ␥-aminobutyric acid (GABA) production, was enriched more than eightfold in A2B5-sorted WMPCs. Although GABA expression has previously not been described in oligodendrocyte lineage cells, glutamate decarboxylase expression by these progenitor cells might have reflected their potential to generate GABAergic neurons when cultured in low density.…”