PDF(Pubmed)
Abstract：
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. Drosophila 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 filamentous actin (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 myocardin-related transcription factor, 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 Smog, G protein αq subunit, Rho1 guanosine triphosphatase, and Diaphanous (Dia)/Formin during NSC reactivation. Further, astrocytes secrete a Smog ligand folded gastrulation to regulate Gαq-Rho1-Dia-mediated NSC reactivation. Together, we establish that the Smog-Gαq-Rho1 signaling axis derived from astrocytes, an NSC niche, regulates Dia-mediated F-actin dynamics in NSC reactivation.
摘要：
神经干细胞（NSC）在静止状态和增殖状态之间的转变是大脑发育和稳态的基础。NSC再激活的缺陷与神经发育障碍有关。果蝇静止的NSC向神经纤维延伸富含肌动蛋白的初级突起。然而,肌动蛋白细胞骨架在NSC再激活过程中的功能尚不清楚。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细丝状肌动蛋白（F-actin）结构。我们表明，F-肌动蛋白聚合促进myocardin相关转录因子的核易位，一种小头畸形相关的转录因子，用于NSC再激活和大脑发育。F-肌动蛋白聚合受由G蛋白偶联受体Smog组成的信号级联调节,G蛋白αq亚基，Rho1鸟苷三磷酸酶，以及NSC重新激活期间的透明（Dia）/Formin。Further,星形胶质细胞分泌Smog配体折叠的胃泌以调节Gαq-Rho1-Dia介导的NSC再激活。一起,我们确定Smog-Gαq-Rho1信号轴来自星形胶质细胞，NSC利基市场，调节NSC再激活中Dia介导的F-肌动蛋白动力学。
