The Proneural GeneMash1Specifies an Early Population of Telencephalic Oligodendrocytes

Abstract

The bHLH (basic helix-loop-helix) transcription factor Mash1 is best known for its role in the regulation of neurogenesis. However, Mash1 is also expressed in oligodendrocyte precursors and has recently been shown to promote the generation of oligodendrocytes in cell culture, suggesting that it may regulate oligodendrogenesis as well. Here, we show that in the developing ventral forebrain, Mash1 is expressed by a subset of oligodendrocyte precursors (OPCs) as soon as they are generated in the ventricular zone. Using reporter mice, we demonstrate that a subset of OPCs in both the embryonic and postnatal forebrain originate from Mash1-positive progenitors, including a large fraction of adult NG2-positive OPCs. Using Mash1 null mutant mice, we show that Mash1 is required for the generation of an early population of OPCs in the ventral forebrain between embryonic day 11.5 (E11.5) and E13.5, whereas OPCs generated later in embryonic development are not affected. Overexpression of Mash1 in the dorsal telencephalon induces expression of PDGFR␣ (platelet-derived growth factor receptor alpha) but not other OPC markers, suggesting that Mash1specifies oligodendrogenesis in cooperation with other factors. Analysis of double-mutant mice suggests that Olig2 is one of the factors that cooperate with Mash1 for generation of OPCs. Together, our results show for the first time that Mash1 cooperates in vivo with Olig2 in oligodendrocyte specification, demonstrating an essential role for Mash1 in the generation of a subset of oligodendrocytes and revealing a genetic heterogeneity of oligodendrocyte lineages in the mouse forebrain.

Down-regulation of the axonal polysialic acid–neural cell adhesion molecule expression coincides with the onset of myelination in the human fetal forebrain

“…The small proportion of Olig2+/PSA-NCAM+ cells probably represents neuronal progenitors, although it is possible that a subpopulation of oligodendrocyte progenitors during very early stages of development expresses PSA-NCAM. This would be consistent with recent reports describing various oligodendrocyte progenitors subpopulations in rodents (Spassky et al, 2000;Kessaris et al, 2006, Parras et al, 2007, and possibly in humans, as we discussed previously (Jakovcevski and Zecevic, 2005b). The fact that at midgestation glia cell populations in the human brain do not express PSA-NCAM, as has been shown in rodents, might be due to either inter-species differences or difference in studied stages of development.…”

In VivoAnalysis of Ascl1 Defined Progenitors Reveals Distinct Developmental Dynamics during Adult Neurogenesis and Gliogenesis

“…Selective expression of GFP in the neurogenic zones in the hippocampus and lateral ventricles, but not in mature neuronal cell layers in the dentate gyrus or olfactory bulb suggests that Ascl1 is transiently expressed during adult neurogenesis. In addition, the extensive, dispersed GFP expression throughout the adult brain including white matter tracts is consistent with recent reports that place Ascl1 in oligodendrocyte precursors (Battiste et al, 2007;Parras et al, 2007;Sugimori et al, 2007).…”

Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination

“…Our studies demonstrate that, at any postnatal age, at least 50% of the NG2 + cells in the SVZ are proliferative and that Cdk2 is a major molecular regulator of their proliferation throughout postnatal development (Belachew et al, 2002;Jablonska et al, 2007). The results of our previous studies also defined the following cellular and molecular properties of NG2 + cells in the SVZ Jablonska et al, 2007): i) NG2 + cells are found scattered through the wall of the lateral ventricle, but they are more abundant in the anterior SVZ; ii) NG2 + cells in the SVZ constitute approximately 12% and 3% of the total cell population at P8 and P30-60, respectively; iii) NG2 + cells in the SVZ are highly proliferative, as demonstrated by the percentages of NG2 + Ki67 + cells in the SVZ -56 and 32% at P8 and P30, respectively; iv) NG2 + cells of the SVZ express cellular markers of neural progenitor cells and stem cells, including the Lewis X antigen (LeX) (Capela and Temple, 2003), and the transcription factors Mash1, Olig2, and Dlx (Doetsch et al, 2002;Parras et al, 2004;Marshall et al, 2005;Menn et al, 2006;Kohwi et al, 2007;Parras et al, 2007); and v) NG2 + cells of the SVZ display a type-C cell phenotype, including expression of the EGFR, PSA-NCAM, and nestin (Capela and Temple, 2002;Doetsch et al, 2002). Consistent with our findings, other reports have also described the presence of NG2 + cells in the SVZ, and demonstrated diverse cellular and molecular properties of these progenitors in this neurogenic region, including co-expression of DCX Tamura et al, 2007), responsiveness to sonic hedgehog (Loulier et al, 2006), and Islet-1-induced migration into striatum (Rogelius et al, 2006).…”