NG2 cells: Properties, progeny and origin

Abstract

The NG2 proteoglycan is a type 1-transmembrane protein expressed by a range of cell types within and outside the mammalian nervous system. NG2-expressing (NG2) cells are found in grey and white matter tracts of the developing and adult CNS and have previously been assumed to represent oligodendrocyte precursor cells: new work using transgenic mice has shown that NG2 cells generate oligodendrocytes, protoplasmic astrocytes and in some instances neurons in vivo. NG2 cells express GABAA receptors and the AMPA subtype of glutamate receptors. They make intimate contact to neurons prior to myelinating axons and also form electron-dense synaptic specialisations with axons in the cerebellum, cortex and hippocampus and with non-myelinated axons in the corpus callosum. These synaptic NG2 cells respond to neuronal release of glutamate and GABA. This neuron-glia interaction may thus regulate the differentiation and proliferation of NG2 cells. The C-terminal PDZ-binding motif of the NG2 protein binds several PDZ proteins including Mupp1, Syntenin and the Glutamate Receptor Interacting Protein (GRIP). Since GRIP can bind subunits of the AMPA receptors expressed by NG2 cells, the interaction between GRIP and NG2 may orientate the glial AMPA receptors towards sites of neuronal glutamate release. The origin, heterogeneity and function of NG2 cells as modulators of the neuronal network are important incompletely resolved questions.

Figure 1. Schematic diagram of the NG2 protein

modified from (Stallcup and Huang, 2008)

Figure 2. The role of the NG2 protein at the neuron-glial synapse

The NG2 protein could play a role in clustering the glial AMPA receptors towards the site of neuronal glutamate release. Glutamate acting on NG2 cells may thus regulate proliferation and differentiation and also cause a rise in intracellular calcium.

Figure 3. Intimate contact between neurons and NG2 cells in the CNS

Confocal image scan of cortex, hippocampus, and cerebellum of adult mice expressing EYFP (A,D,G, J ) stained with an antibody that recognizes Neun (B, E, H, K). Merged images (C, F, I, L) shows no overlap, but close association between EYFP+ cell and Neun + neurons. Inserts at high magnification show EYFP+ cells close to Neun+ neurons. Scale bars = 20 μm

Figure 4. Intimate contact between neurons and NG2 cells in the SVZ and expression of GluR 2/3 by NG2 cells in vivo

Confocal image scan of the SVZ of adult mice expressing EYFP (A), stained with an antibody that recognizes Doublecortin (B). Merged images (C) show no overlap but close association between EYFP+ cells and Doublecortin+ neurons. Hogh magnification inserts show EYFP+ cells very close to Doublecortin + neurons. EYFP+ cells (D) in the juvenile cortex stain with an antibody recognising GluR2/3 (E). Merge and co-localization analysis shows expression of the GluR2/3 on the processes and cell body of the EYFP+ cells. Scale bars = 20 μm

Figure 5. A schematic diagram showing the NG2 cell lineage

NG2 cells originate from NG2−/PDGFRα− cells in the germinal zone and acquire NG2 expression as they migrate to their destination. They have the ability to self-renew and generate oligodendrocytes at all ages. NG2 cells in the immature brain also generate a subpopulation of protoplasmic astrocytes. The neuronal fate of NG2 cells is still debated.