Gαs regulates asymmetric cell division of cortical progenitors by controlling Numb mediated Notch signaling suppression.
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 Gαs 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 Gαs subunit in the cortical progenitor causes an alteration from asymmetric to symmetric cell division, consequently leading to increased progenitor proliferation. Mechanistically, we show that Gαs deletion significantly reduces Numb expression and activates notch signaling. Therefore, these results reveal a novel role of Gαs in control of neural progenitor asymmetric cell division via suppressing Numb mediated Notch signaling inhibition.
West China Developmental and Stem Cell Institute, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China; SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China.
Ke
K
Liu
West China Developmental and Stem Cell Institute, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Quan
Q
Lin
West China Developmental and Stem Cell Institute, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Yanxia
Y
Wei
West China Developmental and Stem Cell Institute, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Renbing
R
He
Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Ximing
X
Shao
Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Zhihao
Z
Ding
Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Jianchao
J
Zhang
SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China.
Minyan
M
Zhu
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Lee S
LS
Weinstein
Department of Cell Biology & Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Yang
Y
Hong
Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China. Electronic address: hc.li@siat.ac.cn.
Hongchang
H
Li
West China Developmental and Stem Cell Institute, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China; SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China; Nerdbio Inc. SIP Biobay, Jiangsu 215213, China. Electronic address: huashunli@tongji.edu.cn.
Huashun
H
Li
D000818:Animals; D002455:Cell Division; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002864:Chromogranins; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
D002864:Chromogranins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; D051880:Receptors, Notch; C498642:Gnas protein, mouse; D019205:GTP-Binding Protein alpha Subunits, Gs
Asymmetric cell division; Gα subunit; Neurogenesis