Neuroscience and Behavioral Disorders Programme, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Mechanobiology Institute, Level 5, T-lab Building, 5A Engineering Drive 1, Singapore, 117411, Singapore.
Sci Adv. 2024 Jul 26;10(30):eadl4694. doi: 10.1126/sciadv.adl4694. Epub 2024 Jul 24.
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 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 α subunit, Rho1 guanosine triphosphatase, and Diaphanous (Dia)/Formin during NSC reactivation. Further, astrocytes secrete a Smog ligand folded gastrulation to regulate Gα-Rho1-Dia-mediated NSC reactivation. Together, we establish that the Smog-Gα-Rho1 signaling axis derived from astrocytes, an NSC niche, regulates Dia-mediated F-actin dynamics in NSC reactivation.
神经干细胞（NSC）在静止和增殖状态之间的转变对于大脑发育和稳态至关重要。NSC 重新激活的缺陷与神经发育障碍有关。静止的 NSC 向神经丛延伸出富含肌动蛋白的初级突起。然而，在 NSC 重新激活过程中肌动蛋白细胞骨架的功能尚不清楚。在这里，我们通过扩展和超分辨率显微镜揭示了静止 NSC 突起中的精细丝状肌动蛋白（F-actin）结构。我们表明，F-actin 的聚合促进了与小头畸形相关的转录因子心肌细胞相关转录因子的核易位，从而促进了 NSC 的重新激活和大脑发育。在 NSC 重新激活过程中，F-actin 的聚合受到由 G 蛋白偶联受体 Smog、G 蛋白α亚基、Rho1 GTP 酶和 Dia/Formin 组成的信号级联调节。此外，星形胶质细胞分泌一种 Smog 配体折叠原肠胚，以调节 Gα-Rho1-Dia 介导的 NSC 重新激活。总之，我们确定了源自星形胶质细胞（NSC 生态位）的 Smog-Gα-Rho1 信号轴调节了 Dia 介导的 NSC 重新激活中的 F-actin 动力学。
