Abstract
ABSTRACTCell geometry is an important element in the regulation of mitotic spindle positioning during early embryo development and tissue morphogenesis. To date, however, we still lack an understanding for how intracellular forces that position and stabilize mitotic spindles depend on cell geometry. Here, we usedin vivomagnetic tweezers to directly measure the forces that maintain the mitotic spindle in the center of sea urchin blastomeres that change sizes and shapes during early embryo development. We found that spindles are held by viscoelastic forces that progressively increase in amplitude at subsequent developmental stages, as cells become smaller and also more elongated in shape. Using simulations, cell shape manipulations and cytoplasm flow analysis, we attribute these mechanical changes to an enhancement of cytoplasm viscoelastic resistance that emerges from stronger hydrodynamic coupling between the spindle and cellular boundaries as cell shapes become more anisotropic. Therefore, this study suggests a novel shape-sensing system for division positioning mediated by cytoplasm hydrodynamics with functional implications for early embryo morphogenesis.Significance StatementThe regulation of mitotic spindle positioning is a key process for tissue architecture, embryo development and stem cells. In many embryos and tissues, cell shape has been proposed to influence the force balance that positions mitotic spindles during cell division. However, direct measurement of the impact of cell geometry on spindle positioning forces are still lacking. Here, using magnetic tweezers to directly measure forces that hold spindles in the cell center, throughout early embryo development, we evidence a direct scaling between cell shape anisotropy and spindle positioning forces. Our data support a model in which the primary effect of cell geometry is to impact the hydrodynamic coupling between the spindle and cell boundaries mediated by the cytoplasm fluid.
Publisher
Cold Spring Harbor Laboratory