Oncotarget

Research Papers:

Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling

Huimin Dong, Xi Lin, Yuntao Li, Ronghua Hu, Yang Xu, Xiaojie Guo, Qiong La, Shun Wang, Congcong Fang, Junli Guo, Qi Li, Shanping Mao and Baohui Liu _

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Oncotarget. 2017; 8:91112-91122. https://doi.org/10.18632/oncotarget.20247

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Abstract

Huimin Dong1,2, Xi Lin3, Yuntao Li4,5, Ronghua Hu6, Yang Xu4, Xiaojie Guo1, Qiong La1, Shun Wang1, Congcong Fang1, Junli Guo7, Qi Li8, Shanping Mao1 and Baohui Liu4

1Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China

2Department of Cell Biology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China

3Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA

4Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China

5Department of Neurosurgery, Huzhou Central Hospital, Huzhou, Zhejiang 313013, China

6Department of Intensive Medicine, Hubei Cancer Hospital, Wuhan, Hubei 430079, China

7Cardiovascular Disease and Research Institute of The First Affiliated Hospital, Key Laboratory of Tropical Diseases and Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, Hainan 571199, China

8Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, China

Correspondence to:

Baohui Liu, email: bliu666@163.com

Shanping Mao, email: maospzy@163.com

Keywords: Rnd3, neural stem cells, Notch signaling, proliferation, stem cells

Received: January 21, 2017     Accepted: July 18, 2017     Published: August 14, 2017

ABSTRACT

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.


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