Determination of neural progenitor cell fate through analyzing microcephaly causative genes.

脊椎动物脑内神经发生的一个标志是极化神经祖细胞的尖-基底核振荡。这些运动与细胞周期同步，在g1期细胞核向基部移动，在g2期细胞核向顶部移动。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通过细胞周期依赖的细胞自主和非自主机制的联系进行。在S - G2过程中，微管相关蛋白Tpx2从细胞核重新分配到根尖过程，并通过改变微管组织促进G2期核迁移。因此，Tpx2与细胞周期进程和自主根尖核迁移有关。相比之下，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期细胞核的基础迁移取决于g2期细胞核向顶端迁移的位移效应。我们的INM模型解释了神经祖细胞的动力学如何使它们的广泛增殖与发育中的大脑上皮结构相协调。此外，我还证明了小头畸形致病基因的基因功能破坏会抑制基底到根尖的活跃核运动。

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 modeling 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. Additionally, I demonstrated that basal to apical active nuclear movement is inhibited by disruption of gene function of microcephaly causative gene.