The perinuclear ER scales nuclear size independently of cell size in early embryos

Abstract

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.3

Cell division geometries as central organizers of early embryo development

“…As observed by Conklin and Wilson in the early 1900's interphasic nuclei also scale with cell volume through embryo development 91,109,110 . However, in difference with spindles, this scaling is partial or non-linear (allometric scaling), with reductions of nuclear volumes being generally slower than reduction in cell volumes, causing progressive increase in nuclear to cytoplasmic (N/C) volume ratio, as embryos develop (Fig.…”

“…(B) In Ascidian embryos, injection of a constitutively active form of myosin phosphatase in some blastomeres can reduce cell contractility changing the shape of neighboring blastomeres and their consequent spindle orientation (Adapted from 40 ). (C) Subcellular control of spindle position using magnetic tweezers and optogenetic tools allows a fine control of subcellular dynein/microtubule forces and consequent position and/or orientation of asters, spindles and division plane (Adapted from 74,109,126 ).…”

“…In addition, accumulation of endomembranes around the nucleus via microtubules and dynein have also been shown to promote nuclear growth and size control 114,115 . For instance, a recent study suggests that the size of the nucleus is correlated with the volume of peri-nuclear endoplasmic reticulum (pER) 109 . As cells divide, this pER pool is gradually partitioned between divided nuclei, independently of cell size, providing one potential mechanism for the different rates of nuclear size and cell size reductions in early embryos.…”

“…Importantly, as nuclear and cell size are uncoupled, an asymmetric division can yield to a net immediate difference in N/C ratios, a process potentially crucial for patterning fate or cell cycle (Fig. 3) 109 .…”

Nuclear sizER in Early Development

“…In this issue of Developmental Cell, Mukherjee et al (2020) investigate control of nuclear growth by live imaging of early embryogenesis, perturbations of blastomere dimensions, and reconstitution in vitro. The authors uncover new mechanisms of nuclear size scaling by the amount of inherited perinuclear ER and duration of interphase.…”