Chia W, Cai Y, Morin X, Tio M, Udolph G, Yu F, Yang X
Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609.
Novartis Found Symp. 2001;237:139-51; discussion 151-63. doi: 10.1002/0470846666.ch11.
Asymmetric cell divisions can be mediated by the preferential segregation of intrinsic cell fate determinants into one of two sibling daughters. In dividing Drosophila neural progenitors the apical-basal orientation of the mitotic spindle, the basal cortical localization of the cell fate determinants Numb and/or Prospero as well as the coordination of these events are mediated by several proteins which include Bazooka (Baz), Inscuteable (Insc) and Partner of Inscuteable (Pins) which localize as an apical cortical complex starting at interphase. Here I will summarize data which suggest that the formation of this apical complex involves two distinct steps: (1) during the initiation of apical complex formation in interphase neuroblasts, there appears to be a hierarchical relation amongst these components where Baz recruits Insc and Baz/Insc in turn recruit Pins to the apical cortex/stalk; (2) while in delaminated mitotic neuroblasts the maintenance of the apical cortical localization of these proteins is dependent on the presence of all three components. Moreover, we show that the maintenance of this apical protein complex is essential for the correct execution of asymmetric division. Finally, the localization of the various asymmetrically localized proteins shows cell cycle dependence; however, the involvement of the cell cycle regulator in asymmetric cell divisions has not been previously shown. Here we present evidence from ongoing experiments which suggest a requirement for the key cell cycle regulator cdc2 in asymmetric cell divisions.
不对称细胞分裂可通过内在细胞命运决定因子优先分离至两个子代姐妹细胞之一来介导。在果蝇神经祖细胞分裂过程中,有丝分裂纺锤体的顶 - 基取向、细胞命运决定因子Numb和/或Prospero的基底部皮质定位以及这些事件的协调由几种蛋白质介导,其中包括Bazooka(Baz)、Inscuteable(Insc)和Inscuteable的伙伴(Pins),它们在间期开始时作为顶皮质复合体定位。在此,我将总结相关数据,这些数据表明该顶复合体的形成涉及两个不同步骤:(1)在间期神经母细胞中顶复合体形成起始阶段,这些组分之间似乎存在层级关系,其中Baz招募Insc,而Baz/Insc依次将Pins招募至顶皮质/柄部;(2)而在分层的有丝分裂神经母细胞中,这些蛋白质的顶皮质定位维持依赖于所有这三种组分的存在。此外,我们表明该顶蛋白复合体的维持对于不对称分裂的正确执行至关重要。最后,各种不对称定位蛋白质的定位显示出细胞周期依赖性;然而,细胞周期调节因子在不对称细胞分裂中的作用此前尚未得到证实。在此,我们展示了正在进行的实验证据,表明关键细胞周期调节因子cdc2在不对称细胞分裂中是必需的。