Differential activation of the DNA replication checkpoint contributes to asynchrony of cell division in C-elegans embryos
Differential activation of the DNA replication checkpoint contributes to asynchrony of cell division in C-elegans embryos
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DOI：
10.1016/s0960-9822(03)00295-1
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发表时间：
2003-05-13
期刊：
影响因子：
9.2
通讯作者：
Gönczy, P
中科院分区：
文献类型：
--
作者：
Brauchle, M;Baumer, K;Gönczy, P
背景：获得谱系特异性细胞周期持续时间是后生动物发育的核心特征。人们对早期胚胎发生过程中实现这一目标的机制知之甚少。在线虫秀丽隐杆线虫中，细胞周期持续时间的差异从双细胞阶段开始就很明显，此时较大的前卵裂球 AB 在较小的后卵裂球 P-1 之前分裂。前后 (A-P) 极性线索如何控制这种异步仍有待阐明。结果：我们确定早期秀丽隐杆线虫胚胎具有迄今为止未被识别的 DNA 复制检查点，该检查点依赖于 PIl-3 样激酶 atl-1 和激酶 chk-1。我们证明，P-1 卵裂球中这个检查点的优先激活有助于两细胞阶段野生型胚胎中细胞分裂的异步。此外，我们发现，在 Galpha 信号失活后经历相同的首次卵裂的胚胎中，优先检查点激活在很大程度上被消除。结论：我们的研究结果表明，差异检查点激活有助于获得两细胞阶段的秀丽隐杆线虫胚胎中不同的细胞周期持续时间，并提出了一种将不对称分裂与发育过程中不同细胞周期持续时间的获取相结合的新机制。
Background: Acquisition of lineage-specific cell cycle duration is a central feature of metazoan development. The mechanisms by which this is achieved during early embryogenesis are poorly understood. In the nematode Caenorhabditis elegans, differential cell cycle duration is apparent starting at the two-cell stage, when the larger anterior blastomere AB divides before the smaller posterior blastomere P-1. How anterior-posterior (A-P) polarity cues control this asynchrony remains to be elucidated.Results: We establish that early C. elegans embryos possess a hitherto unrecognized DNA replication checkpoint that relies on the PIl-3-like kinase atl-1 and the kinase chk-1. We demonstrate that preferential activation of this checkpoint in the P-1 blastomere contributes to asynchrony of cell division in two-cell-stage wildtype embryos. Furthermore, we show that preferential checkpoint activation is largely abrogated in embryos that undergo equal first cleavage following inactivation of Galpha signaling.Conclusion: Our findings establish that differential checkpoint activation contributes to acquisition of distinct cell cycle duration in two-cell-stage C. elegans embryos and suggest a novel mechanism coupling asymmetric division to acquisition of distinct cell cycle duration during development.