Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Cell. 2013 Sep 12;154(6):1300-13. doi: 10.1016/j.cell.2013.08.024.
Radial glial progenitors (RGPs) are elongated epithelial cells that give rise to neurons, glia, and adult stem cells during brain development. RGP nuclei migrate basally during G1, apically using cytoplasmic dynein during G2, and undergo mitosis at the ventricular surface. By live imaging of in utero electroporated rat brain, we find that two distinct G2-specific mechanisms for dynein nuclear pore recruitment are essential for apical nuclear migration. The "RanBP2-BicD2" and "Nup133-CENP-F" pathways act sequentially, with Nup133 or CENP-F RNAi arresting nuclei close to the ventricular surface in a premitotic state. Forced targeting of dynein to the nuclear envelope rescues nuclear migration and cell-cycle progression, demonstrating that apical nuclear migration is not simply correlated with cell-cycle progression from G2 to mitosis, but rather, is a required event. These results reveal that cell-cycle control of apical nuclear migration occurs by motor protein recruitment and identify a role for nucleus- and centrosome-associated forces in mitotic entry. PAPERCLIP:
放射状胶质前体细胞 (RGPs) 是长形的上皮细胞,在大脑发育过程中产生神经元、神经胶质和成人干细胞。RGPs 核在 G1 期基底迁移,在 G2 期使用细胞质动力蛋白顶极迁移,并在脑室表面进行有丝分裂。通过对宫内电穿孔大鼠脑的实时成像,我们发现两种不同的 G2 特异性动力蛋白核孔募集机制对于顶端核迁移至关重要。“RanBP2-BicD2”和“Nup133-CENP-F”途径依次作用,Nup133 或 CENP-F RNAi 将核阻滞在接近脑室表面的有丝分裂前期。强制将动力蛋白靶向核膜可挽救核迁移和细胞周期进程,表明顶端核迁移与从 G2 到有丝分裂的细胞周期进程并非简单相关,而是必需事件。这些结果揭示了细胞周期对顶端核迁移的控制是通过马达蛋白募集发生的,并确定了核和中心体相关力在有丝分裂进入中的作用。