RT Journal Article SR Electronic T1 Cytoplasmic volume and limiting nucleoplasmin scale nuclear size during Xenopus laevis development JF bioRxiv FD Cold Spring Harbor Laboratory SP 511451 DO 10.1101/511451 A1 Pan Chen A1 Miroslav Tomschik A1 Katherine Nelson A1 John Oakey A1 J. C. Gatlin A1 Daniel L. Levy YR 2019 UL http://biorxiv.org/content/early/2019/01/03/511451.abstract AB How nuclear size is regulated relative to cell size is a fundamental cell biological question. Reductions in both cell and nuclear sizes during Xenopus laevis embryogenesis provide a robust scaling system to study mechanisms of nuclear size regulation. To test if the volume of embryonic cytoplasm is limiting for nuclear growth, we encapsulated gastrula stage embryonic cytoplasm and nuclei in droplets of defined volume using microfluidics. Nuclei grew and reached new steady-state sizes as a function of cytoplasmic volume, supporting a limiting component mechanism of nuclear size control. Through biochemical fractionation, we identified the histone chaperone nucleoplasmin (Npm2) as a putative nuclear size-scaling factor. Cellular amounts of Npm2 decrease over development, and nuclear size was sensitive to Npm2 levels both in vitro and in vivo, affecting nuclear histone levels and chromatin organization. Thus, reductions in cell volume with concomitant decreases in Npm2 amounts represent a developmental mechanism of nuclear size-scaling that may also be relevant to cancers with increased nuclear size.AbbreviationsNEnuclear envelope;NPCnuclear pore complex;ERendoplasmic reticulum;NLSnuclear localization signal;PKCprotein kinase C;CScross-sectional;N/Cnuclear-to-cytoplasmic;MBTmidblastula transition;Npm2nucleoplasmin