A Cell Size-Dependent Competition Between Geometry and Polarity Governs Nuclear and Spindle positioning in Early Embryos

Nuclei and mitotic spindles are actively positioned at defined locations within cells to regulate cell polarity, division and multicellular morphogenesis1-4. Forces generated by cytoskeleton networks regulate the positioning of these organelles and are commonly influenced by extrinsic cues such as cell geometry or polarity5-12. To date, however, most studies have investigated this problem in one given cell type, hampering our understanding for how mechanical systems that position nuclei and spindles may scale during multicellular development. We tracked the spatiotemporal behaviour of centrosomes, nuclei and spindles in early sea urchin embryos from the 1-cell to the [~]1000 cells blastula stage. We found that they are initially located at cell centers, but that they undergo a progressive decentration towards the embryo apical surface, as cells become smaller during development. This apical shift is mediated by microtubule (MTs) pulling forces which are influenced by both cell shapes and apical polarity domains. Using 3D mathematical models and embryo dissections, we propose that MT centering forces that derive from cell geometry decay in strength during development as a consequence of cell size reduction, allowing apical polarity decentering forces to take over. 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.