Gαs regulates asymmetric cell division of cortical progenitors by controlling Numb mediated Notch signaling suppression

被引:7
作者
Liu, Ke [1 ,2 ,3 ]
Lin, Quan [1 ,2 ]
Wei, Yanxia [1 ,2 ]
He, Renbing [1 ,2 ]
Shao, Ximing [3 ]
Ding, Zhihao [3 ]
Zhang, Jianchao [3 ]
Zhu, Minyan [4 ]
Weinstein, Lee S. [6 ]
Hong, Yang [7 ]
Li, Hongchang [3 ]
Li, Huashun [1 ,2 ,3 ,4 ,5 ]
机构
[1] Sichuan Univ, West China Hosp 2, West China Dev & Stem Cell Inst, Chengdu 610064, Peoples R China
[2] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610064, Peoples R China
[3] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab Mol Biol Neural Dev, Lab Dev & Regenerat Biol,Inst Biomed & Biotechnol, Shenzhen 518055, Guangdong, Peoples R China
[4] Tongji Univ, Sch Med, Shanghai East Hosp, SARITEX Ctr Stem Cell Engn Translat Med, Shanghai 200123, Peoples R China
[5] Nerdbio Inc, SIP Biobay, Nanjing 215213, Jiangsu, Peoples R China
[6] NIDDK, NIH, Bethesda, MD 20892 USA
[7] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA
基金
美国国家科学基金会;
关键词
G alpha subunit; Neurogenesis; Asymmetric cell division; GNAS GENE-PRODUCTS; NERVOUS-SYSTEM; FATE SPECIFICATION; NEUROGENESIS; POLARITY; NEURONS; LOCALIZATION; CDC42; APKC; PAR6;
D O I
10.1016/j.neulet.2015.04.034
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Asymmetric cell division, which plays fundamental roles in generating cell diversity during development, requires elaborate interactions between extrinsic cues and intrinsic cues. However, the precise nature of this type of interaction and its involving signaling mechanisms are poorly understood. Here, we demonstrate that Gas is present in the proliferative region of ventricular zone in mouse developing neocortex and co-localizes with intrinsic cell fate determinant protein Numb in dividing apical progenitors. Targeted ablation of Gas subunit in the cortical progenitor causes an alteration from asymmetric to symmetric cell division, consequently leading to increased progenitor proliferation. Mechanistically, we show that Gas deletion significantly reduces Numb expression and activates notch signaling. Therefore, these results reveal a novel role of Gas in control of neural progenitor asymmetric cell division via suppressing Numb mediated Notch signaling inhibition. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:97 / 103
页数:7
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