Lin Kun-Yang, Gujar Mahekta R, Lin Jiaen, Ding Wei Yung, Huang Jiawen, Gao Yang, Tan Ye Sing, Teng Xiang, Christine Low Siok Lan, Kanchanawong Pakorn, Toyama Yusuke, Wang Hongyan
bioRxiv. 2024 Mar 13:2024.03.11.584337. doi: 10.1101/2024.03.11.584337.
The transitioning of neural stem cells (NSCs) between quiescent and proliferative states is fundamental for brain development and homeostasis. Defects in NSC reactivation are associated with neurodevelopmental disorders. quiescent NSCs extend an actin-rich primary protrusion toward the neuropil. However, the function of the actin cytoskeleton during NSC reactivation is unknown. Here, we reveal the fine F-actin structures in the protrusions of quiescent NSCs by expansion and super-resolution microscopy. We show that F-actin polymerization promotes the nuclear translocation of Mrtf, a microcephaly-associated transcription factor, for NSC reactivation and brain development. F-actin polymerization is regulated by a signaling cascade composed of G-protein-coupled receptor (GPCR) Smog, G-protein αq subunit, Rho1 GTPase, and Diaphanous (Dia)/Formin during NSC reactivation. Further, astrocytes secrete a Smog ligand Fog to regulate Gαq-Rho1-Dia-mediated NSC reactivation. Together, we establish that the Smog-Gαq-Rho1 signaling axis derived from astrocytes, a NSC niche, regulates Dia-mediated F-actin dynamics in NSC reactivation.
神经干细胞（NSCs）在静止状态和增殖状态之间的转变对于大脑发育和内环境稳定至关重要。神经干细胞重新激活过程中的缺陷与神经发育障碍有关。静止的神经干细胞向神经毡延伸出富含肌动蛋白的初级突起。然而，肌动蛋白细胞骨架在神经干细胞重新激活过程中的功能尚不清楚。在这里，我们通过扩展和超分辨率显微镜揭示了静止神经干细胞突起中的精细F-肌动蛋白结构。我们表明，F-肌动蛋白聚合促进小头畸形相关转录因子Mrtf的核转位，以实现神经干细胞的重新激活和大脑发育。在神经干细胞重新激活过程中，F-肌动蛋白聚合受由G蛋白偶联受体（GPCR）Smog、G蛋白αq亚基、Rho1 GTP酶和双盘状蛋白（Dia）/Formin组成的信号级联调节。此外，星形胶质细胞分泌Smog配体Fog来调节Gαq-Rho1-Dia介导的神经干细胞重新激活。我们共同确定，源自神经干细胞微环境星形胶质细胞的Smog-Gαq-Rho1信号轴在神经干细胞重新激活过程中调节Dia介导的F-肌动蛋白动力学。
