Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone.
Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone.
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DOI：
10.1083/jcb.200702031
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发表时间：
2007-12-17
期刊：
影响因子：
--
通讯作者：
Gallo V
中科院分区：
文献类型：
--
作者：
Jablonska B;Aguirre A;Vandenbosch R;Belachew S;Berthet C;Kaldis P;Gallo V
我们研究了出生后发育过程中神经前体细胞中细胞周期蛋白依赖性激酶2（Cdk 2）的功能。脑室下区（SVZ）的硫酸软骨素蛋白聚糖（NG 2）表达祖细胞在围产期Cdk 2 −/−和野生型小鼠之间的密度和增殖没有显着差异，仅在成年Cdk 2 −/−小鼠中减少。培养中的成年Cdk 2 −/− SVZ细胞显示自我更新能力下降和分化增强。围产期Cdk 2 −/− SVZ细胞的代偿机制持续到出生后第15天，涉及Cdk 4表达增加，导致视网膜母细胞瘤蛋白失活。出生后第28天Cdk 2 −/−细胞中Cdk 4活性随后下降至野生型水平，与较低的NG 2+增殖和自我更新能力相一致，与成人水平相似。围产期Cdk 2 −/− SVZ细胞中的Cdk 4沉默消除了Cdk 4上调，并将细胞增殖和自我更新降低到成人水平。相反，Cdk 4在成年SVZ细胞中的过表达将增殖能力恢复到野生型水平。因此，虽然Cdk 2在围产期SVZ中是功能冗余的，但它对于通过Cdk 4的年龄依赖性调节的成体祖细胞增殖和自我更新是重要的。
We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)–expressing progenitor cells of the subventricular zone (SVZ) show no significant difference in density and proliferation between Cdk2−/− and wild-type mice at perinatal ages and are reduced only in adult Cdk2−/− mice. Adult Cdk2−/− SVZ cells in culture display decreased self-renewal capacity and enhanced differentiation. Compensatory mechanisms in perinatal Cdk2−/− SVZ cells, which persist until postnatal day 15, involve increased Cdk4 expression that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4 activity to wild-type levels in postnatal day 28 Cdk2−/− cells coincides with lower NG2+ proliferation and self-renewal capacity similar to adult levels. Cdk4 silencing in perinatal Cdk2−/− SVZ cells abolishes Cdk4 up-regulation and reduces cell proliferation and self- renewal to adult levels. Conversely, Cdk4 overexpression in adult SVZ cells restores proliferative capacity to wild-type levels. Thus, although Cdk2 is functionally redundant in perinatal SVZ, it is important for adult progenitor cell proliferation and self-renewal through age-dependent regulation of Cdk4.
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影响因子：
10.5
作者：
LaBaer, J;Garrett, MD;Harlow, E
通讯作者：
Harlow, E
影响因子：
7.8
作者：
Aguirre, Adan A;Chittajallu, Ramesh;Belachew, Shibeshih;Gallo, Vittorio
通讯作者：
Gallo, Vittorio
影响因子：
10.5
作者：
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通讯作者：
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影响因子：
9.2
作者：
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通讯作者：
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影响因子：
5.3
作者：
Aguirre, A;Gallo, V
通讯作者：
Gallo, V