Tio M, Udolph G, Yang X, Chia W
Institute of Molecular and Cell Biology, Singapore.
Nature. 2001 Feb 22;409(6823):1063-7. doi: 10.1038/35059124.
Asymmetric cell divisions can be mediated by the preferential segregation of cell-fate determinants into one of two sibling daughters. In Drosophila neural progenitors, Inscuteable, Partner of Inscuteable and Bazooka localize as an apical cortical complex at interphase, which directs the apical-basal orientation of the mitotic spindle as well as the basal/cortical localization of the cell-fate determinants Numb and/or Prospero during mitosis. Although localization of these proteins shows dependence on the cell cycle, the involvement of cell-cycle components in asymmetric divisions has not been demonstrated. Here we show that neural progenitor asymmetric divisions require the cell-cycle regulator cdc2. By attenuating Drosophila cdc2 function without blocking mitosis, normally asymmetric progenitor divisions become defective, failing to correctly localize asymmetric components during mitosis and/or to resolve distinct sibling fates. cdc2 is not necessary for initiating apical complex formation during interphase; however, maintaining the asymmetric localization of the apical components during mitosis requires Cdc2/B-type cyclin complexes. Our findings link cdc2 with asymmetric divisions, and explain why the asymmetric localization of molecules like Inscuteable show cell-cycle dependence.
不对称细胞分裂可由细胞命运决定因子优先分离至两个子代细胞之一来介导。在果蝇神经祖细胞中，无翅型原钙黏蛋白、无翅型原钙黏蛋白伴侣及巴祖卡蛋白在间期定位于顶端皮质复合体，该复合体在有丝分裂期间指导有丝分裂纺锤体的顶-基取向以及细胞命运决定因子麻木蛋白和/或 prospero 蛋白的基底/皮质定位。尽管这些蛋白质的定位显示出对细胞周期的依赖性，但细胞周期成分在不对称分裂中的作用尚未得到证实。在此，我们表明神经祖细胞不对称分裂需要细胞周期调节因子 cdc2。通过在不阻断有丝分裂的情况下减弱果蝇 cdc2 的功能，正常的不对称祖细胞分裂会出现缺陷，在有丝分裂期间无法正确定位不对称成分和/或区分不同的子代细胞命运。cdc2 对于在间期启动顶端复合体的形成不是必需的；然而，在有丝分裂期间维持顶端成分的不对称定位需要 Cdc2/B 型细胞周期蛋白复合体。我们的研究结果将 cdc2 与不对称分裂联系起来，并解释了为何像无翅型原钙黏蛋白这样的分子的不对称定位表现出细胞周期依赖性。
