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

• Published in: Neuroscience letters Vol. 597; pp. 97 - 103
• Main Authors: Liu, Ke, Lin, Quan, Wei, Yanxia, He, Renbing, Shao, Ximing, Ding, Zhihao, Zhang, Jianchao, Zhu, Minyan, Weinstein, Lee S., Hong, Yang, Li, Hongchang, Li, Huashun
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 15.06.2015
• Subjects: Animals; Asymmetric cell division; Cell Division; Cell Proliferation; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Cerebral Cortex - metabolism; Chromogranins; GTP-Binding Protein alpha Subunits, Gs - metabolism; Gα subunit; Membrane Proteins - metabolism; Mice; Neocortex - cytology; Neocortex - embryology; Neocortex - metabolism; Nerve Tissue Proteins - metabolism; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurogenesis; Receptors, Notch - metabolism; Signal Transduction; Neurogenesis; Gα subunit; Asymmetric cell division
• DOI: 10.1016/j.neulet.2015.04.034
• ISSN: 0304-3940

•The ablation of Gαs in cortical progenitors impairs VZ development and increased cortical progenitor proliferation.•Gαs inactivation causes a shift from asymmetric cell division to symmetric cell division of cortical progenitors.•Gαs co-localizes with cell polarity protein Numb and inhibits Notch signaling pathway in cortical development. 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.