Lis1/dynactin regulates metaphase spindle orientation in Drosophila neuroblasts.
Lis1/dynactin regulates metaphase spindle orientation in Drosophila neuroblasts.
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DOI：
10.1016/j.ydbio.2008.03.018
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发表时间：
2008-07
影响因子：
2.7
通讯作者：
K. Siller;C. Doe
中科院分区：
文献类型：
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作者：
K. Siller;C. Doe
极化细胞有丝分裂纺锤体的取向决定了它们是对称分裂还是不对称分裂。此外，调节纺锤体取向可能对胚胎发育、干细胞生物学和肿瘤生长很重要。果蝇神经母细胞沿顶端/基底皮质极性轴排列纺锤体，使顶端神经母细胞自我更新并产生基底分化细胞。目前尚不清楚纺锤体的定位是否需要顶端和基部的信号，也没有发现调节纺锤体运动的分子马达。利用完整幼虫大脑内神经母细胞的实时成像，我们检测到顶端和基部纺锤体极点的独立运动，表明力同时作用于两极。我们发现，减少星状微管会降低主轴运动的频率，但不会降低其最大速度，这表明一个或几个微管可以移动主轴。Lis1/dynactin复合体的突变体强烈降低纺锤体的最大和平均速度，这与该运动复合体介导纺锤体/皮层力一致。星体微管或Lis1/动肌蛋白的缺失会导致中期纺锤体/皮质极性排列缺陷，但这些缺陷会在末期得到修复。我们提出早期的Lis1/动力蛋白依赖通路和晚期的Lis1/动力蛋白不依赖通路调节神经母细胞纺锤体取向。
Mitotic spindle orientation in polarized cells determines whether they divide symmetrically or asymmetrically. Moreover, regulated spindle orientation may be important for embryonic development, stem cell biology, and tumor growth. Drosophila neuroblasts align their spindle along an apical/basal cortical polarity axis to self-renew an apical neuroblast and generate a basal differentiating cell. It is unknown whether spindle alignment requires both apical and basal cues, nor have molecular motors been identified that regulate spindle movement. Using live imaging of neuroblasts within intact larval brains, we detect independent movement of both apical and basal spindle poles, suggesting that forces act on both poles. We show that reducing astral microtubules decreases the frequency of spindle movement, but not its maximum velocity, suggesting that one or few microtubules can move the spindle. Mutants in the Lis1/dynactin complex strongly decrease maximum and average spindle velocity, consistent with this motor complex mediating spindle/cortex forces. Loss of either astral microtubules or Lis1/dynactin leads to spindle/cortical polarity alignment defects at metaphase, but these are rescued by telophase. We propose that an early Lis1/dynactin-dependent pathway and a late Lis1/dynactin-independent pathway regulate neuroblast spindle orientation.