Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe, Japan.
EMBO J. 2011 May 4;30(9):1690-704. doi: 10.1038/emboj.2011.81. Epub 2011 Mar 25.
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.
神经发生在脊椎动物大脑中的一个标志是极化神经祖细胞中的顶端-基底核振荡。这种运动被称为核周运动（interkinetic nuclear migration，INM），与细胞周期同步，使得核在 G1 期向基底移动，在 G2 期向顶端移动。然而，目前尚不清楚运动的方向和细胞周期是如何紧密结合的。在这里，我们表明 INM 通过细胞自主和非自主机制的细胞周期依赖性连接进行。在 S 期到 G2 期进展过程中，微管相关蛋白 Tpx2 从核重新分布到顶端过程，并通过改变微管组织促进 G2 期核迁移。因此，Tpx2 将细胞周期进展和自主顶端核迁移联系起来。相比之下，对植入微珠的体内观察、周围细胞的急性 S 期阻滞和计算模型表明，G1 期核的基底迁移依赖于向顶端迁移的 G2 期核的位移效应。我们的 INM 模型解释了神经祖细胞的动力学如何使它们的大量增殖与发育中大脑的上皮结构协调一致。
