A cell size-dependent competition between geometry and polarity governs nuclear and spindle positioning in early...

Nuclei and mitotic spindles are actively positioned at defined locations within cells to regulate cell polarity, division, and multicellular morphogenesis.^1,2,3,4 Forces generated by cytoskeleton networks regulate the positioning of these organelles and are commonly influenced by extrinsic cues, such as cell geometry or polarity.^{5,6,7,8,9,10,11,12} To date, however, most studies have investigated this problem in one given cell type, hampering our understanding of how mechanical systems that position nuclei and spindles may scale during multicellular development. We tracked the spatiotemporal behavior of centrosomes, nuclei, and spindles in early sea urchin embryos from the 1-cell to the ∼1,000-cell blastula stage. We found that they are initially located at cell centers, but that they undergo a progressive decentration toward the embryo apical surface, as cells become smaller during development. This apical shift is mediated by microtubule (MT) pulling forces, which are influenced by both cell shapes and apical polarity domains. Using 3D mathematical models and embryo dissections, we propose that apical cortical polarity MT decentering forces progressively take over centering forces during development as a consequence of cell size reduction and resulting increase in surface-to-volume ratio. Our results support a self-organized scenario in which polarity cues progressively outcompete cell geometry to modulate the overall balance of MT forces and pattern nuclear and spindle positioning throughout early embryo development.