The Silencing Effect of microRNA miR-17 on p21 Maintains the Neural Progenitor Pool in the Developing Cerebral Cortex.
The Silencing Effect of microRNA miR-17 on p21 Maintains the Neural Progenitor Pool in the Developing Cerebral Cortex.
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DOI：
10.3389/fneur.2014.00132
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发表时间：
2014
影响因子：
3.4
通讯作者：
Sun T
中科院分区：
文献类型：
--
作者：
Chen Y;Bian S;Zhang J;Zhang H;Tang B;Sun T
发育中的大脑皮层中神经祖细胞库的扩大对于控制大脑大小至关重要，因为增殖缺陷与人类小头畸形的发病机制有关。细胞周期调控因子在神经前体细胞增殖中起重要作用。在这里，我们表明，细胞周期蛋白依赖性激酶抑制剂p21（也称为Cdkn 1a和Cip 1）负调节放射状胶质细胞（RGCs）和中间祖细胞（IP）在胚胎小鼠皮层的增殖。microRNA-17（miR-17）与p21在发育中的皮质中显示相互表达。与p21相反，miR-17促进RGCs和IP的扩增，如通过过表达miR-17前体和可敲低内源性miR-17的miR-17海绵所证明的。此外，p21是通常被miR-17沉默的推定靶点。miR-17与p21的共表达足以挽救p21对祖细胞增殖的负调控。我们的研究结果表明了控制神经祖细胞库的机制，即在发育中的皮质中通过miR-17抑制p21。
Expansion of the neural progenitor pool in the developing cerebral cortex is crucial for controlling brain size, since proliferation defects have been associated with the pathogenesis of microcephaly in humans. Cell cycle regulators play important roles in proliferation of neural progenitors. Here, we show that the cyclin-dependent kinase inhibitor p21 (also called Cdkn1a and Cip1) negatively regulates proliferation of radial glial cells (RGCs) and intermediate progenitors (IPs) in the embryonic mouse cortex. MicroRNA-17 (miR-17) displays reciprocal expressions with p21 in the developing cortex. Opposite to p21, miR-17 promotes expansion of RGCs and IPs, as demonstrated by overexpressing miR-17 precursors and miR-17 sponges that can knock down the endogenous miR-17. Moreover, p21 is a putative target normally silenced by miR-17. Co-expression of miR-17 with p21 is sufficient to rescue the negative regulation of p21 on progenitor proliferation. Our results indicate a mechanism of controlling the neural progenitor pool, which is to suppress p21 by miR-17 in the developing cortex.
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影响因子：
8.8
作者：
Bian S;Hong J;Li Q;Schebelle L;Pollock A;Knauss JL;Garg V;Sun T
通讯作者：
Sun T
影响因子：
7.3
作者：
Gibcus, Johan H.;Kroesen, Bart-Jan;van den Berg, Anke
通讯作者：
van den Berg, Anke
DOI：
10.1073/pnas.0308600100
发表时间：
2004-03-02
影响因子：
11.1
作者：
Haubensak, W;Attardo, A;Huttner, WB
通讯作者：
Huttner, WB
影响因子：
48
作者：
Gentner, Bernhard;Schira, Giulia;Naldini, Luigi
通讯作者：
Naldini, Luigi
影响因子：
10.5
作者：
Arnold, Sebastian J.;Huang, Guo-Jen;Groszer, Matthias
通讯作者：
Groszer, Matthias