PLK-1 asymmetry contributes to asynchronous cell division of C. elegans embryos
PLK-1 asymmetry contributes to asynchronous cell division of C. elegans embryos
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DOI：
10.1242/dev.019075
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发表时间：
2008-04-01
期刊：
影响因子：
4.6
通讯作者：
Goenczy, Pierre
中科院分区：
文献类型：
--
作者：
Budirahardja, Yemima;Goenczy, Pierre
获得谱系特异性细胞周期持续时间是后生动物发育的一个重要特征。在秀丽隐杆线虫中，细胞周期持续时间的差异在两细胞期胚胎中已经很明显，当较大的前卵裂球AB在较小的后卵裂球P-1之前分裂。这种时间差是由PAR蛋白设定的前后（A-P）极性线索控制的。这些线索在AB和P-1中调控细胞周期机制的差异机制尚不完全清楚。先前的研究表明，P-1细胞分裂的延迟部分是由于P-1中ATL-1/CHK-1依赖性检查点的优先激活，但如何控制剩余的时差尚不清楚。在这里，我们确定了不同的时间也依赖于一种机制，这种机制优先促进AB有丝分裂的发生。polo样激酶PLK-1是有丝分裂进入的正调节因子，在两细胞期胚胎中以不对称的方式分布，AB中存在的蛋白质比P-1中更多。我们发现PLK-1的不对称性是由A-P极性线索通过胚胎前部的优先蛋白保留来调节的。重要的是，RNAi对plk-1的轻度失活延迟了P-1的有丝分裂，而不是AB，其方式与ATL-1/CHK-1无关。总之，我们的研究结果支持了秀丽隐杆线虫胚胎有丝分裂进入的不同时间依赖于两种互补机制的模型：P-1依赖于ATL-1/ chk -1的优先延迟和AB依赖于plk -1的优先促进，它们在早期发育过程中将极性线索和细胞周期进程结合在一起。
Acquisition of lineage-specific cell cycle duration is an important feature of metazoan development. In Caenorhabditis elegans, differences in cell cycle duration are already apparent in two-cell stage embryos, when the larger anterior blastomere AB divides before the smaller posterior blastomere P-1. This time difference is under the control of anterior-posterior ( A-P) polarity cues set by the PAR proteins. The mechanisms by which these cues regulate the cell cycle machinery differentially in AB and P-1 are incompletely understood. Previous work established that retardation of P-1 cell division is due in part to preferential activation of an ATL-1/CHK-1 dependent checkpoint in P-1, but how the remaining time difference is controlled is not known. Here, we establish that differential timing relies also on a mechanism that promotes mitosis onset preferentially in AB. The polo-like kinase PLK-1, a positive regulator of mitotic entry, is distributed in an asymmetric manner in two-cell stage embryos, with more protein present in AB than in P-1. We find that PLK-1 asymmetry is regulated by A-P polarity cues through preferential protein retention in the embryo anterior. Importantly, mild inactivation of plk-1 by RNAi delays entry into mitosis in P-1, but not in AB, in a manner that is independent of ATL-1/CHK-1. Together, our findings support a model in which differential timing of mitotic entry in C. elegans embryos relies on two complementary mechanisms: ATL-1/CHK-1-dependent preferential retardation in P-1 and PLK-1-dependent preferential promotion in AB, which together couple polarity cues and cell cycle progression during early development.