GSK3β Regulates Oligodendrogenesis in the Dorsal Microdomain of the Subventricular Zone via Wnt- β- catenin Signaling
GSK3β Regulates Oligodendrogenesis in the Dorsal Microdomain of the Subventricular Zone via Wnt- β- catenin Signaling
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DOI：
10.1002/glia.22641
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发表时间：
2014-05-01
期刊：
影响因子：
6.2
通讯作者：
Butt, Arthur M.
中科院分区：
文献类型：
--
作者：
Azim, Kasum;Rivera, Andrea;Butt, Arthur M.
少突胶质细胞是中枢神经系统的髓鞘形成细胞，出生后源自室下区 (SVZ) 的少突胶质细胞前体 (OP)。然而，人们对调节 SVZ 神经干细胞 (NSC) 生成的机制知之甚少。在这里，我们研究了糖原合成酶激酶 3 (GSK3) 的作用，它是出生后小鼠中多种汇聚信号通路的效应器。 rt-qPCR 检测的 GSK3 表达在 SVZ 和发育中的白质中最为突出，大约在出生后的前 1-2 周，与 OP 分化的高峰期一致。出生后 (P) 8-11 天的小鼠脑室内注射 GSK3 抑制剂 ARA-014418 显着增加了 SVZ 背侧微区中 OP 的生成，如使用 rt-qPCR 和免疫标记检测细胞特异性标记物的表达所示。对阶段特异性标记物的分析表明，OP 的增强是通过早期 SVZ 细胞类型的规格增加而发生的。 GSK3 抑制对背侧 SVZ 的这些影响很大程度上归因于对经典 Wnt/-catenin 信号通路的刺激，而不是其他通路。结果表明，GSK3 是在 Wnt 信号传导控制下特异性调节背侧 SVZ 微区少突胶质细胞发生的关键内源因子。 GLIA 2014；62：778-789
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 3 (GSK3), an effector of multiple converging signaling pathways in postnatal mice. The expression of GSK3by 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 GSK3 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 GSK3 inhibition on the dorsal SVZ were largely attributable to stimulation of the canonical Wnt/-catenin signaling pathway over other pathways. The results indicate GSK3 is a key endogenous factor for specifically regulating oligodendrogenesis from the dorsal SVZ microdomain under the control of Wnt-signaling. GLIA 2014;62:778-789