Interaction between NG2 proteoglycan and PDGF ?-receptor on O2A progenitor cells is required for optimal response to PDGF

Abstract

Previous studies on the NG2 chondroitin sulfate proteoglycan have shown that NG2 is expressed on A2B5‐positive O2A progenitor cells, which are known to respond to platelet‐derived growth factor (PDGF). In the accompanying paper (Nishiyama et al.; J Neurosci Res 43:299–314, 1996) we show that on O2A progenitors in the embryonic and newborn rat brain, NG2 and PDGF α‐receptor display an extensive co‐localization which becomes less pronounced as the brain matures past the first postnatal week. The present communication describes the relationship between NG2 and PDGF α‐receptor in vitro. NG2 and PDGF α‐receptor are highly co‐localized on A2B5‐positive O2A cells isolated from neonatal rat cerebrum. Mimicking the situation in vivo, the level of expression of the two molecules and the extent of co‐localization decline as these cells differentiate into O4‐positive pre‐oligodendrocytes. However, maintenance of the cells in a progenitor state by treatment with bFGF results in increased levels of both NG2 and PDGF α‐receptor on the cell surface, suggesting that expression of the two molecules may be coordinately regulated. Furthermore, NG2 can be co‐immunoprecipitated from radiolabeled O2A extracts with a rabbit antibody to PDGF α‐receptor, indicating the presence of a molecular complex that includes NG2 and the receptor. Finally, antibody‐patching and subsequent down‐regulation of NG2 results in reduced expression of PDGF α‐receptor and diminishes the proliferative response of the cells to PDGF. These findings suggest that correct co‐expression of the NG2 proteoglycan and PDGF α‐receptor on the surface of O2A progenitor cells is important for the cells' ability to respond effectively to the mitogenic stimulus of PDGF. © 1996 Wiley‐Liss, Inc.

Oligodendrocyte precursor hypercellularity and abnormal retina development in mice overexpressing PDGF‐B in myelinating tracts

“…The increase in PDGF ␣-receptor mRNA hybridization signal in transgenic corpus callosum and cerebellar medulla, compared to controls, reveals that the increase in cell number is at least in part due to generation of more oligodendrocytes. Staining with antibodies to the proteoglycan NG2, which colocalizes with PDGF ␣-receptor on oligodendrocyte precursors in vitro and in vivo (Nishiyama et al, 1996a(Nishiyama et al, , 1996b, revealed an increase also of NG2 immunoreactivity in MBP-PDGF-B mice, thus confirming these cells as O2A progenitors.…”

A role for the NG2 proteoglycan in glioma progression

“…treatment with anti-NG2 antibody inhibited proliferation of oligodendrocyte progenitors. 43 Subsequently, we showed that, whereas the combined action of FGF2 and PDGF-AA was able to maintain wild type progenitors in their undifferentiated state, NG2 null progenitors began the process of differentiation even in the presence of the two growth factors. 119 More careful work done with aortic smooth muscle cells showed that NG2 null cells failed to proliferate or migrate normally in response to PDGF-AA, due to poor activation of PDGFRα.…”

“…Along with PDGFRα, NG2 has become one of the most reliable markers for these progenitors. 4,[41][42][43][44][45][46] In keeping with general observations regarding NG2 expression, the proteoglycan is not expressed by multipotent neural stem cells in primary and secondary germinal zones of the central nervous system, but is upregulated on progenitors that emerge from these germinal zones and are committed to the oligodendrocyte lineage. Through a program of proliferation and migration, oligodendrocyte progenitors populate the entire central nervous system and differentiate into myelinating oligodendrocytes.…”

Glial Progenitors in Adult White Matter Are Driven to Form Malignant Gliomas by Platelet-Derived Growth Factor-Expressing Retroviruses

“…5, 6). PDGFR␣ϩ/NG2ϩ glial progenitors are abundant and widely distributed in the subcortical white matter of adult humans and rodents (Gogate et al, 1994;Nishiyama et al, 1996;Scolding et al, 1998;Dawson et al, 2000). As with our model, human gliomas grow by diffusely infiltrating the brain and the tumor cells intermingle with normal brain cells.…”