Cullin-5 mutants reveal collective sensing of the nucleocytoplasmic ratio in Drosophila embryogenesis.
Cullin-5 mutants reveal collective sensing of the nucleocytoplasmic ratio in Drosophila embryogenesis.
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DOI：
10.1016/j.cub.2022.03.007
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发表时间：
2022-05-09
期刊：
影响因子：
9.2
通讯作者：
Di Talia, Stefano
中科院分区：
文献类型：
--
作者：
Hayden, Luke;Chao, Anna;Deneke, Victoria E.;Vergassola, Massimo;Puliafito, Alberto;Di Talia, Stefano
在大多数后生动物中，早期胚胎发育的特征是快速分裂周期，在囊胚中期过渡（MBT）的原肠胚形成之前暂停。这些分裂伴随着细胞骨架重排，以确保正确的核定位。然而，控制核定位的分子机制尚未完全阐明。在果蝇中，早期胚胎发生在多核合胞体中展开。在细胞周期4-6，细胞核在肌动球蛋白收缩性和细胞质流动的驱动下快速移动穿过前后（AP）轴。在shackleton（shkl）突变体中，这种轴向伸展受到损害。在这里，我们表明shkl突变携带cullin-5（cul-5）基因突变。活体成像实验表明，Cul-5是细胞周期的下游，但需要皮质肌动球蛋白收缩。cul-5突变体的核扩散表型可以通过降低Src活性来挽救，这表明Cul-5的主要靶标是Src激酶。cul-5突变体显示出跨越AP轴的核密度梯度，我们利用该梯度来研究作为N/C比的函数的细胞周期控制。我们发现，N/C比在大约100μm的邻域内被集体感知，这种集体感知是精确的MBT所必需的，在MBT中，胚胎中的所有核暂停其分裂周期。此外，我们发现，N/C比的响应沿AP轴沿着略微分级。这两个特征可以与Cdk 1动力学联系起来。总的来说，我们揭示了一个新的途径控制核定位，并提供了一个解剖核周期如何响应N/C比。Hayden等人表明，泛素连接酶Cullin-5对果蝇胚胎中皮层肌动球蛋白收缩性和核定位很重要。此外，作者揭示，决定核延长细胞周期在中期囊胚过渡是在大集体和介导的Cdk 1反应扩散动力学。
In most metazoans, early embryonic development is characterized by rapid division cycles which pause before gastrulation at the mid-blastula transition (MBT). These cleavage divisions are accompanied by cytoskeletal rearrangements which ensure proper nuclear positioning. Yet, the molecular mechanisms controlling nuclear positioning are not fully elucidated. In Drosophila, early embryogenesis unfolds in a multinucleated syncytium. Nuclei rapidly move across the anterior-posterior (AP) axis at cell cycles 4–6 in a process driven by actomyosin contractility and cytoplasmic flows. In shackleton (shkl) mutants, this axial spreading is impaired. Here, we show that shkl mutants carry mutations in the cullin-5 (cul-5) gene. Live imaging experiments show that Cul-5 is downstream of the cell cycle but required for cortical actomyosin contractility. The nuclear spreading phenotype of cul-5 mutants can be rescued by reducing Src activity, suggesting that a major target of Cul-5 is Src kinase. cul-5 mutants display gradients of nuclear density across the AP axis which we exploit to study cell cycle control as a function of the N/C ratio. We found that the N/C ratio is sensed collectively in neighborhoods of about 100μm and such collective sensing is required for a precise MBT in which all the nuclei in the embryo pause their division cycle. Moreover, we found that the response to the N/C ratio is slightly graded along the AP axis. These two features can be linked to Cdk1 dynamics. Collectively, we reveal a new pathway controlling nuclear positioning and provide a dissection of how nuclear cycles respond to the N/C ratio. Hayden et al show that the ubiquitin ligase Cullin-5 is important for cortical actomyosin contractility and nuclear positioning in Drosophila embryos. Moreover, the authors reveal that the decision of nuclei to lengthen the cell cycle at the mid-blastula transition is made in large collectives and mediated by Cdk1 reaction-diffusion dynamics.
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