Aurora A inhibition disrupts chromosome condensation and spindle assembly during the first embryonic division in pigs
Aurora A inhibition disrupts chromosome condensation and spindle assembly during the first embryonic division in pigs
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DOI：
10.1111/rda.13655
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发表时间：
2020-02-29
影响因子：
1.7
通讯作者：
Ju，Shiqiang
中科院分区：
文献类型：
--
作者：
Cui，Panpan;Abbasi，Benazir;Ju，Shiqiang
由于Aurora A在多种肿瘤中的普遍过表达，其在肿瘤诱导中的作用及其在肿瘤治疗中的价值已引起人们的广泛关注，但其在哺乳动物胚胎第一次卵裂分裂中的作用却知之甚少。在这里，我们强调了极光A在猪胚胎减数分裂后的第一次有丝分裂过程中不可或缺的作用。通过Western blot和间接免疫荧光染色初步研究了Aurora A在猪胚胎第一次有丝分裂中的表达和时空定位。然后，使用高选择性Aurora A抑制剂MLN 8054进一步评价Aurora A在猪胚胎有丝分裂过程中的潜在作用。Aurora A在猪胚胎第一次有丝分裂过程中表达并表现出特定的动态细胞内定位模式。Aurora A在分裂前期扩散到细胞质中，然后在随后的有丝分裂期表现出与染色体和纺锤体动态密切相关的动态细胞内定位。MLN 8054处理对Aurora A的抑制导致第一次卵裂失败，大多数胚胎在有丝分裂前期停滞。进一步的亚细胞结构检查显示，Aurora A抑制不仅导致纺锤体微管组装失败，还导致染色体凝聚严重缺陷，伴随着第一次有丝分裂前期p-TACC 3（S558）表达的明显下降。总之，这些结果表明，Aurora A在猪胚胎第一次有丝分裂期间对纺锤体组装和染色体凝聚至关重要，并且Aurora A的调节可能与其对p-TACC 3（S558）表达的影响有关。
As common overexpression of Aurora A in various tumours, much attention has focused on its function in inducing cancer, and its value in cancer therapeutics, considerably less is known regarding its role in the first cleavage division of mammalian embryos. Here, we highlight an indispensable role of Aurora A during the first mitotic division progression of pig embryos just after meiosis. The expression and spatiotemporal localization of Aurora A were initially assessed in pig embryos during the first mitotic division by Western blot analysis and indirect immunofluorescent staining. Then, the potential role of Aurora A was further evaluated using a highly selective Aurora A inhibitor, MLN8054, during this mitotic progression in pig embryos. Aurora A was found to express and exhibit a specific dynamic intracellular localization pattern during the first mitotic division in pig embryos. Aurora A was diffused in the cytoplasm at the prophase stage, and then exhibited a dynamic intracellular localization which was tightly associated with the chromosome and spindle dynamics throughout subsequent mitotic phases. Inhibition of Aurora A by MLN8054 treatment led to the failure of the first cleavage, with the majority of embryos being arrested in prophase of the mitotic division. Further subcellular structure examination showed that Aurora A inhibition not only led to the failure of spindle microtubule assembly, but also resulted in severe defects in chromosome condensation, accompanied by an obvious decrease in p‐TACC3(S558) expression during the prophase of the first mitosis. Together, these results illustrated that Aurora A is crucial for both spindle assembly and chromosome condensation during the first mitotic division in pig embryos, and that the regulation of Aurora A may be associated with its effects on p‐TACC3(S558) expression.