Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain.
Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain.
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DOI：
10.1038/emboj.2011.81
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发表时间：
2011-05-04
期刊：
影响因子：
11.4
通讯作者：
Matsuzaki, Fumio
中科院分区：
文献类型：
--
作者：
Kosodo, Yoichi;Suetsugu, Taeko;Suda, Masumi;Mimori-Kiyosue, Yuko;Toida, Kazunori;Baba, Shoji A.;Kimura, Akatsuki;Matsuzaki, Fumio
脊椎动物脑中神经发生的标志是极化神经祖细胞中的顶-基底核振荡。这些运动被称为运动间核迁移（INM），与细胞周期同步，使得细胞核在G1期期间向基底移动，在G2期期间向顶部移动。然而，目前尚不清楚运动方向和细胞周期是如何紧密耦合的。在这里，我们表明，INM收益通过细胞周期依赖的细胞自主和非自主机制的联系。在S到G2的进程中，微管相关蛋白Tpx 2从细胞核重新分布到顶突，并通过改变微管组织在G2期促进细胞核迁移。因此，Tpx 2链接细胞周期进程和自主顶端核迁移。相比之下，在体内观察植入的微珠，周围细胞的急性S期阻滞和计算建模表明，G1期细胞核的基底迁移取决于G2期细胞核顶部迁移的位移效应。我们的INM模型解释了神经祖细胞的动态如何协调其广泛的增殖与发育中的大脑上皮结构。
A hallmark of neurogenesis in the vertebrate brain is the apical–basal nuclear oscillation in polarized neural progenitor cells. Known as interkinetic nuclear migration (INM), these movements are synchronized with the cell cycle such that nuclei move basally during G1-phase and apically during G2-phase. However, it is unknown how the direction of movement and the cell cycle are tightly coupled. Here, we show that INM proceeds through the cell cycle-dependent linkage of cell-autonomous and non-autonomous mechanisms. During S to G2 progression, the microtubule-associated protein Tpx2 redistributes from the nucleus to the apical process, and promotes nuclear migration during G2-phase by altering microtubule organization. Thus, Tpx2 links cell-cycle progression and autonomous apical nuclear migration. In contrast, in vivo observations of implanted microbeads, acute S-phase arrest of surrounding cells and computational modelling suggest that the basal migration of G1-phase nuclei depends on a displacement effect by G2-phase nuclei migrating apically. Our model for INM explains how the dynamics of neural progenitors harmonize their extensive proliferation with the epithelial architecture in the developing brain.
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