Endogenous Neural Stem Cell Mediated Oligodendrogenesis in the Adult Mammalian Brain

Abstract

Oligodendrogenesis is essential for replacing worn-out oligodendrocytes, promoting myelin plasticity, and for myelin repair following a demyelinating injury in the adult mammalian brain. Neural stem cells are an important source of oligodendrocytes in the adult brain; however, there are considerable differences in oligodendrogenesis from neural stem cells residing in different areas of the adult brain. Amongst the distinct niches containing neural stem cells, the subventricular zone lining the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus are considered the principle areas of adult neurogenesis. In addition to these areas, radial glia-like cells, which are the precursors of neural stem cells, are found in the lining of the third ventricle, where they are called tanycytes, and in the cerebellum, where they are called Bergmann glia. In this review, we will describe the contribution and regulation of each of these niches in adult oligodendrogenesis.

Keywords: Bergmann glia; adult neural stem cell; cerebellum; oligodendrocyte; oligodendrogenesis; subgranular zone; subventricular zone; tanycyte.

Figure 1

Stages of neural stem cells and their markers. The different stages of neural stem cells (NSCs) are identified by expression of markers and level of proliferation. Only activated NSCs (aNSCs) and transit-amplifying progenitors (TAPs) grow as neurospheres and differentiate into the oligodendroglial, astroglial, and neuronal lineages in vitro. OPC, oligodendrocyte progenitor cell.

Figure 2

Neural stem cells in the adult subventricular zone (SVZ), hippocampal subgranular zone (SGZ), and the lining of the third ventricle. Gli1 NSCs were fate-mapped by tamoxifen injection in the adult (P60-80) Gli1CreER;Ai9 mice and analyzed by immunofluorescence for GFAP (green) to detect NSCs, TdT (magenta) to detect Gli1 fate-mapped cells, and Hoechst (blue) to detect cell nuclei, 2 weeks after tamoxifen administration. The right panels are higher magnification views of the dotted boxes in the left panels. The arrows indicate the area in the coronal brain sections from Allen brain atlas. Scale bar = 50 μm.

Figure 3

Bergmann glia in the adult cerebellum. Gli1-expressing Bergmann glia were fate-mapped by tamoxifen injection in the adult (P60-80) Gli1CreER;Ai9 mice and analyzed by immunofluorescence to detect TdT-positive (red) Gli1 fate-mapped cells and Hoechst (blue)-positive cell nuclei, 2 weeks after tamoxifen administration.