Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
Université de Paris, Centre National de la Recherche Scientifique, Institut Jacques Monod, F-75006, Paris, France.
Dev Cell. 2020 Aug 10;54(3):395-409.e7. doi: 10.1016/j.devcel.2020.05.003. Epub 2020 May 29.
Nuclear size plays pivotal roles in gene expression, embryo development, and disease. A central hypothesis in organisms ranging from yeast to vertebrates is that nuclear size scales to cell size. This implies that nuclei may reach steady-state sizes set by limiting cytoplasmic pools of size-regulating components. By monitoring nuclear dynamics in early sea urchin embryos, we found that nuclei undergo substantial growth in each interphase, reaching a maximal size prior to mitosis that declined steadily over the course of development. Manipulations of cytoplasmic volume through multiple chemical and physical means ruled out cell size as a major determinant of nuclear size and growth. Rather, our data suggest that the perinuclear endoplasmic reticulum, accumulated through dynein activity, serves as a limiting membrane pool that sets nuclear surface growth rate. Partitioning of this local pool at each cell division modulates nuclear growth kinetics and dictates size scaling throughout early development.
核大小在基因表达、胚胎发育和疾病中起着关键作用。从酵母到脊椎动物等生物的一个中心假设是,核大小与细胞大小成比例。这意味着核可能达到由大小调节成分的细胞质池限制所确定的稳定大小。通过监测早期海胆胚胎中的核动态,我们发现核在每个间期中都经历了大量的生长,在有丝分裂前达到最大大小,然后在发育过程中稳步下降。通过多种化学和物理手段对细胞质体积的操纵排除了细胞大小作为核大小和生长的主要决定因素。相反,我们的数据表明,通过动力蛋白活性积累的核周内质网充当限制膜池,从而设定核表面生长速率。在每次细胞分裂时对这个局部池的分区调节核生长动力学,并决定整个早期发育过程中的大小缩放。