Early embryonic NG2 glia are exclusively gliogenic and do not generate neurons in the brain

Abstract

In the central nervous system, the type I transmembrane glycoprotein NG2 (nerve‐glia antigen 2) is only expressed by pericytes and oligodendrocyte precursor cells (OPCs). Therefore, OPCs are also termed NG2 glia. Their fate during development has been investigated systematically in several genetically modified mouse models. Consensus exists that postnatal NG2 glia are restricted to the oligodendrocyte (OL) lineage, while, at least in the forebrain, embryonic NG2 glia could also generate astrocytes. In addition, experimental evidence for a neurogenic potential of NG2 glia in the early embryonic brain (before E16.5) has been provided. However, this observation is still controversial. Here, we took advantage of reliable transgene expression in NG2‐EYFP and NG2‐CreERT2 knock‐in mice to study the fate of early embryonic NG2 glia. While pericytes were the main cells with robust NG2 gene activity at E12.5, only a few OPCs expressed NG2 at this early stage of embryogenesis. Subsequently, this proportion of OPCs increased from 3% (E12.5) to 11% and 25% at E14.5 and E17.5, respectively. When Cre DNA recombinase activity was induced at E12.5 and E14.5 and pups were analyzed at postnatal day 0 (P0) and P10, the vast majority of recombined cells, besides pericytes, belonged to the OL lineage cells, with few astrocytes in the ventral forebrain. In other brain regions such as brain stem, cerebellum, and olfactory bulb only OL lineage cells were detected. Therefore, we conclude that NG2 glia from early embryonic brain are restricted to a gliogenic fate and do not differentiate into neurons after birth.

Oligodendrocyte lineage cells and depression

“…In addition, in PDGFRα-CreER T2 ;RosaYFP double-transgenic adult mice, a small number of YFP+ neurons could be detected in the forebrain, especially in the piriform cortex, which is the main projection target of the olfactory bulb [35]. However, another study reported that early embryonic OPCs are restricted to the OL lineage and cannot generate neurons in the cerebellum, brain stem or olfactory bulb [36]. These contradictory observations necessitate further indepth investigation in the field.…”

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

“…During development, oligodendrocyte progenitor cells (OPCs; expressing the markers PDGFRα and NG2) are first observed in the ventricular germinal zones of the brain and spinal cord at embryonic day 12.5 (E12.5) in mice (Huang, Guo, Bai, Scheller, & Kirchhoff, ; Pringle & Richardson, ; Timsit et al, ; Warf, Fok‐Seang, & Miller, ) while a second wave of these cells originate from the dorsal cord at E15.5 (Cai et al, ; Fogarty, Richardson, & Kessaris, ; Vallstedt, Klos, & Ericson, ). Ultimately, these two populations of OPCs display similar properties (Marques et al, ; Tripathi et al, ) and both differentiate to form the myelinating cell of the central nervous system (CNS), the oligodendrocyte.…”

Cell Progeny in the Olfactory Bulb after Targeting Specific Progenitors with Different UbC-StarTrack Approaches

“…This tool also allows progenitor cells to be tracked in vivo, avoiding genetic manipulation of the animals or viral injections. In our particular case, NSCs in the LV were targeted by IUE, avoiding targeting progenitor cells at other sites in which these promoters may be active, such as pericytes in the case of the NG2 promoter [34][35][36]. NG2-hyPBase-driven integration of the StarTrack mix via IUE targets those neural progenitors in the LV with an active NG2-promoter, thereby limiting the developmental spatio-temporal parameters of the study (reviewed by Shimogory and Ogawa [37]).…”