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出生后小鼠脑室下区内表达血小板源性生长因子β受体的神经祖细胞的特征分析

Characterization of neuroprogenitor cells expressing the PDGF beta-receptor within the subventricular zone of postnatal mice.

作者信息

Ishii Yoko, Matsumoto Yoshiki, Watanabe Rie, Elmi Muna, Fujimori Toshihiko, Nissen Johan, Cao Yihai, Nabeshima Yo-Ichi, Sasahara Masakiyo, Funa Keiko

机构信息

Institute of Biomedicine, Department of Medical Chemistry and Cell Biology, Göteborg University, Box 420, SE 405 30 Gothenburg, Sweden.

出版信息

Mol Cell Neurosci. 2008 Mar;37(3):507-18. doi: 10.1016/j.mcn.2007.11.006. Epub 2007 Dec 3.

Abstract

We report a considerable number of cells in the ventricular and the subventricular zones (SVZ) of newborn mice to stain positive for the PDGF beta-receptor (PDGFRB). Many of them also stained for nestin and/or GFAP but less frequently for the neuroblast marker doublecortin and for the mitotic marker Ki-67. The SVZ of mice with nestin-Cre conditional deletion of PDGFRB expressed the receptor only on blood vessels and was devoid of any morphological abnormality. PDGFRB(-/-) neurospheres showed a higher rate of apoptosis without any significant decrease in proliferation. They demonstrated reduced capacities of migration and neuronal differentiation in response to not only PDGF-BB but also bFGF. Furthermore, the PDGFR kinase inhibitor STI571 blocked the effects of bFGF in control neurosphere cultures. bFGF increased the activity of the PDGFRB promoter as well as the expression and phosphorylation of PDGFRB. These results suggest the presence of the signaling convergence between PDGF and FGF. PDGFRB is needed for survival, and the effects of bFGF in migration and neural differentiation of the cells may be potentiated by induction of PDGFRB.

摘要

我们报告称,新生小鼠脑室及脑室下区(SVZ)中有相当数量的细胞对血小板衍生生长因子β受体(PDGFRB)呈阳性染色。其中许多细胞也对巢蛋白和/或胶质纤维酸性蛋白(GFAP)呈阳性染色,但对神经母细胞标志物双皮质素和有丝分裂标志物Ki-67呈阳性染色的频率较低。巢蛋白-Cre条件性缺失PDGFRB的小鼠的SVZ仅在血管上表达该受体,且无任何形态学异常。PDGFRB(-/-)神经球显示出较高的凋亡率,而增殖无显著降低。它们不仅对血小板衍生生长因子-BB(PDGF-BB),而且对碱性成纤维细胞生长因子(bFGF)的迁移和神经元分化能力均降低。此外,PDGFR激酶抑制剂STI571阻断了bFGF在对照神经球培养物中的作用。bFGF增加了PDGFRB启动子的活性以及PDGFRB的表达和磷酸化。这些结果表明血小板衍生生长因子(PDGF)和碱性成纤维细胞生长因子(FGF)之间存在信号转导汇聚。PDGFRB对细胞存活是必需的,并且bFGF在细胞迁移和神经分化中的作用可能通过诱导PDGFRB而增强。

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