Glia. 2014 May;62(5):778-9. doi: 10.1002/glia.22641.
Oligodendrocytes, the myelinating cells of the CNS, are derived postnatally from oligodendrocyte precursors (OPs) of the subventricular zone (SVZ). However, the mechanisms that regulate their generation from SVZ neural stem cells (NSC) are poorly understood. Here, we have examined the role of glycogen synthase kinase 3β (GSK3β), an effector of multiple converging signaling pathways in postnatal mice. The expression of GSK3β by rt-qPCR was most prominent in the SVZ and in the developing white matter, around the first 1–2 weeks of postnatal life, coinciding with the peak periods of OP differentiation. Intraventricular infusion of the GSK3β inhibitor ARA-014418 in mice aged postnatal day (P) 8–11 significantly increased generation of OPs in the dorsal microdomain of the SVZ, as shown by expression of cell specific markers using rt-qPCR and immunolabelling. Analysis of stage specific markers revealed that the augmentation of OPs occurred via increased specification from earlier SVZ cell types. These effects of GSK3β inhibition on the dorsal SVZ were largely attributable to stimulation of the canonical Wnt/β-catenin signaling pathway over other pathways. The results indicate GSK3β is a key endogenous factor for specifically regulating oligodendrogenesis from the dorsal SVZ microdomain under the control of Wnt-signaling.
少突胶质细胞是中枢神经系统的髓鞘形成细胞，它们在后生性地来源于脑室下区 (SVZ) 的少突胶质前体细胞 (OPs)。然而，调节它们从 SVZ 神经干细胞 (NSC) 产生的机制尚不清楚。在这里，我们研究了糖原合成酶激酶 3β (GSK3β) 的作用，GSK3β 是多种汇聚信号通路在出生后小鼠中的效应物。通过 rt-qPCR 检测到 GSK3β 的表达在 SVZ 和正在发育的白质中最为显著，在出生后的第一周到第二周左右，这与 OPs 分化的高峰期一致。在出生后第 8-11 天的小鼠中，脑室内输注 GSK3β 抑制剂 ARA-014418 显著增加了 SVZ 背侧微区 OPs 的生成，这通过 rt-qPCR 和免疫标记检测到细胞特异性标记物的表达来证实。对阶段特异性标记物的分析表明，OPs 的增加是通过来自早期 SVZ 细胞类型的特异性增加来实现的。GSK3β 抑制对 SVZ 背侧的这些影响主要归因于对经典 Wnt/β-catenin 信号通路的刺激，而不是对其他通路的刺激。这些结果表明 GSK3β 是一个关键的内源性因子，在 Wnt 信号的控制下，特异性地调节 SVZ 背侧微区的少突胶质发生。
