Lineage, fate, and fate potential of NG2-glia

Abstract

NG2 cells represent a fourth major glial cell population in the mammalian central nervous system (CNS). They arise from discrete germinal zones in mid-gestation embryos and expand to occupy the entire CNS parenchyma. Genetic fate mapping studies have shown that oligodendrocytes and a subpopulation of ventral protoplasmic astrocytes arise from NG2 cells. This review describes recent findings on the fate and fate potential of NG2 cells under physiological and pathological conditions. We discuss age-dependent changes in the fate and fate potential of NG2 cells and possible mechanisms that could be involved in restricting their oligodendrocyte differentiation or fate plasticity. This article is part of a Special Issue entitled SI:NG2-glia(Invited only).

Keywords: Cell fate; Lineage; Myelin; NG2; Oligodendrocyte; Polydendrocyte.

Figure 1. Distribution and morphology of NG2 cells in the neonate and adult

A–B. P0 mouse telencephalon labeled for NG2 (green) and Olig2 (blue). A. Low magnification tiled image of the distribution of NG2 cells. Note the higher density in the nascent white matter and deeper cortical layers and the presence of many Olig2+ NG2- cells in the SVZ. B. Higher magnification of the region boxed in A showing the morphology of individual NG2 cells. NG2 is also highly expressed on the vasculature. Left is medial, top is dorsal. Arrow: a multiprocessed cell. Arrowheads: a cell with asymmetric long processes. svz: subventricular zone. C–E. P60 telencephalon labeled for NG2 (green) and Olig2 (blue). C. Low magnification view spanning the neocortex and corpus callosum. D. Superficial layer of the cortex. E. Junction of corpus callosum and neocortex. NG2 cells with similar morphology are similarly distributed in superficial and deep neocortical layers but there are more NG2-negative Olig2+ cells (arrows in E), which are likely to be oligodendrocytes, in deeper layers. ctx: neocortex; cc: corpus callosum Scale bars, A and C 100 μm, B, D, and E 20 μm.

Figure 2. Scheme showing the lineage and fate of NG2 cells

A. Relationship between NG2 cells and the entire oligodendrocyte lineage. Left: A cartoon showing the appearance of NG2 cells in the parenchyma (blue shade) after specification of the oligodendrocyte lineage in the germinal zone (ventricular zone, gray shade). NG2 cells (blue cells with processes) expand while some generate protoplasmic astrocytes (green cells with bushy morphology). Right: A diagram depicting the chronology of oligodendrocyte lineage specification and differentiation. Blue shade denotes “committed oligodendrocyte” lineage cells. A subpopulation of these cells with all the molecular signatures of oligodendrocyte lineage cells downregulate and become protoplasmic astrocytes (green). B. Diagrams highlighting the unanswered question of whether all NG2 cells are capable of differentiating into oligodendrocytes. B1 proposes a scenario in which all NG2 cells are equivalent in their ability to become oligodendrocytes. B2 proposes the alternative possibility of two segregated populations of NG2 cells: one with oligodendrogliogenic potential (blue dots) and the other without (red dots).