Inhibition of Plk1 induces mitotic infidelity and embryonic growth defects in developing zebrafish embryos
Inhibition of Plk1 induces mitotic infidelity and embryonic growth defects in developing zebrafish embryos
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DOI：
10.1016/j.ydbio.2010.06.004
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发表时间：
2010-09-01
影响因子：
2.7
通讯作者：
Lee, Hyunsook
中科院分区：
文献类型：
--
作者：
Jeong, KilHun;Jeong, Jae-Yeon;Lee, Hyunsook
Polo样激酶1（Plk1）是细胞分裂的核心。在这里，我们报告说，Plk 1是至关重要的有丝分裂在斑马鱼胚胎发育。使用几种细胞生物学工具的组合，包括应用于整个胚胎的单细胞活体成像，我们表明Plk 1在胚胎发育过程中对有丝分裂的进展至关重要。Plk1变形细胞表现出有丝分裂不忠实，如异常的中心体，不规则的纺锤体装配，超浓缩的染色体，和染色体臂分离失败。因此，Plk1的耗竭导致有丝分裂停滞，并最终在受精后6天死亡。相比之下，Plk2或Plk3变形体胚胎未显示任何显著异常。用Plk1抑制剂BI 2536处理胚胎，导致有丝分裂阻滞，当用于处理plk1 morphants时，这种情况更为严重。最后，使用一种分析来拯救Plk1变形表型，我们发现激酶结构域和PBD结构域都是必要的Plk1功能在斑马鱼的发展我们的研究表明，Plk1是必需的胚胎增殖，因为它的活性是至关重要的有丝分裂的完整性。此外，我们的研究表明，斑马鱼将是一个有效的和经济的体内系统，用于验证抗有丝分裂药物。(C)2010年爱思唯尔公司All rights reserved.
Polo-like kinase 1 (Plk1) is central to cell division. Here, we report that Plk1 is critical for mitosis in the embryonic development of zebrafish. Using a combination of several cell biology tools, including single-cell live imaging applied to whole embryos, we show that Plk1 is essential for progression into mitosis during embryonic development. Plk1 morphant cells displayed mitotic infidelity, such as abnormal centrosomes, irregular spindle assembly, hypercondensed chromosomes, and a failure of chromosome arm separation. Consequently, depletion of Plk1 resulted in mitotic arrest and finally death by 6 days post-fertilization. In comparison, Plk2 or Plk3 morphant embryos did not display any significant abnormalities. Treatment of embryos with the Plk1 inhibitor, BI 2536, caused a block in mitosis, which was more severe when used to treat plk1 morphants. Finally, using an assay to rescue the Plk1 morphant phenotype, we found that the kinase domain and PBD domains are both necessary for Plk1 function in zebrafish development Our studies demonstrate that Plk1 is required for embryonic proliferation because its activity is crucial for mitotic integrity. Furthermore, our study suggests that zebrafish will be an efficient and economical in vivo system for the validation of anti-mitotic drugs. (C) 2010 Elsevier Inc. All rights reserved.