Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling.
Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling.
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神经干细胞中 Rnd3 的基因缺失通过上调 Notch 信号传导促进增殖
DOI：
10.18632/oncotarget.20247
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发表时间：
2017-10-31
期刊：
影响因子：
--
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Dong H;Lin X;Li Y;Hu R;Xu Y;Guo X;La Q;Wang S;Fang C;Guo J;Li Q;Mao S;Liu B
Rnd3是一种Rho GT3，通过Rho激酶依赖的信号通路参与肌动蛋白细胞骨架动力学的抑制。我们先前证明，与野生型小鼠相比，Rnd3基因缺失的小鼠发育出明显更大的大脑。在这里，我们证明了Rnd3基因敲除小鼠开发了一个扩大的脑室下区，我们确定了一个新的作用Rnd3作为抑制剂的Notch信号在神经干细胞。Rnd3缺陷，在体内和体外，导致Notch细胞内结构域蛋白的水平增加。这导致增强的Notch信号传导和促进异常神经干细胞生长，从而导致更大的脑室下区和明显更大的大脑。Notch活性的抑制消除了这种异常的神经干细胞生长。
Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro, resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.