Dong Huimin, Lin Xi, Li Yuntao, Hu Ronghua, Xu Yang, Guo Xiaojie, La Qiong, Wang Shun, Fang Congcong, Guo Junli, Li Qi, Mao Shanping, Liu Baohui
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
Department of Cell Biology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Oncotarget. 2017 Aug 14;8(53):91112-91122. doi: 10.18632/oncotarget.20247. eCollection 2017 Oct 31.
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 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that 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. deficiency, both and , 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.
Rnd3是一种Rho GTP酶，通过Rho激酶依赖的信号通路参与对肌动蛋白细胞骨架动力学的抑制。我们之前证明，基因缺失的小鼠与野生型小鼠相比，大脑明显更大。在此，我们证明Rnd3基因敲除小鼠的脑室下区增大，并且我们确定了Rnd3在神经干细胞中作为Notch信号抑制剂的新作用。Rnd3缺失导致Notch细胞内结构域蛋白水平升高，这导致Notch信号增强并促进异常神经干细胞生长，从而导致脑室下区更大和大脑明显更大。抑制Notch活性可消除这种异常神经干细胞生长。
