Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Dev Cell. 2014 Dec 8;31(5):559-71. doi: 10.1016/j.devcel.2014.10.023.
During the development of the nervous system, apicobasally polarized stem cells are characterized by a shorter cell cycle than nonpolar progenitors, leading to a lower differentiation potential of these cells. However, how polarization might be directly linked to the kinetics of the cell cycle is not understood. Here, we report that apicobasally polarized neuroepithelial cells in Xenopus laevis have a shorter cell cycle than nonpolar progenitors, consistent with mammalian systems. We show that the apically localized serine/threonine kinase aPKC directly phosphorylates an N-terminal site of the cell-cycle inhibitor p27Xic1 and reduces its ability to inhibit the cyclin-dependent kinase 2 (Cdk2), leading to shortening of G1 and S phases. Overexpression of activated aPKC blocks the neuronal differentiation-promoting activity of p27Xic1. These findings provide a direct mechanistic link between apicobasal polarity and the cell cycle, which may explain how proliferation is favored over differentiation in polarized neural stem cells.
在神经系统的发育过程中，与非极性祖细胞相比，顶端-基底极性的干细胞具有更短的细胞周期，导致这些细胞的分化潜力降低。然而，极化如何直接与细胞周期的动力学相关联尚不清楚。在这里，我们报告说，非洲爪蟾的顶端-基底极性神经上皮细胞的细胞周期比非极性祖细胞更短，这与哺乳动物系统一致。我们表明，顶端定位的丝氨酸/苏氨酸激酶 aPKC 直接磷酸化细胞周期抑制剂 p27Xic1 的 N 端位点，并降低其抑制周期蛋白依赖性激酶 2（Cdk2）的能力，导致 G1 和 S 期缩短。激活的 aPKC 的过表达阻断了 p27Xic1 促进神经元分化的活性。这些发现为顶端-基底极性和细胞周期之间提供了直接的机制联系，这可能解释了为什么在极化的神经干细胞中增殖优先于分化。
