Nuclear size may therefore play important roles in normal development and cell physiology as well as disease. Furthermore, increased nuclear size is almost uniformly used for cancer diagnosis and prognosis ( Jevtić and Levy, 2014 Zink et al., 2004). Nuclear size control is of particular interest, as there are dramatic reductions in nuclear size during early development ( Hara et al., 2013 Jevtić and Levy, 2015) and nuclear size tends to scale with cell size in different species and cell types ( Conklin, 1912 Wilson, 1925). We propose that reductions in cell volume and the amounts of limiting components, such as Npm2, contribute to developmental nuclear size scaling.Ī fundamental question in cell biology is how organelle sizes are regulated. 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. Through biochemical fractionation, we identified the histone chaperone nucleoplasmin (Npm2) as a putative nuclear size effector. Nuclei grew and reached new steady-state sizes as a function of cytoplasmic volume, supporting a limiting component mechanism of nuclear size control. 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. Reductions in both cell and nuclear sizes during Xenopus laevis embryogenesis provide a robust scaling system to study mechanisms of nuclear size regulation. How nuclear size is regulated relative to cell size is a fundamental cell biological question.
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