LET-99-dependent spatial restriction of active force generators makes spindle's position robust

Background: During asymmetric division of the Caenorhabditis elegans nematode zygote, the polarity cues distribution and daughter cell fates depend on the correct positioning of the mitotic spindle which results from both centering and cortical pulling forces. Revealed by spindle rocking, these pulling forces are regulated by the force generator dynamics, which are related to mitosis progression. This may be combined with a second regulation, this one by the posterior spindle pole position, which can be seen when comparing related species. Results: After delaying anaphase onset, we identified a positional pulling force regulation in C. elegans, which we ascribed to microtubule dynamics at the cortex. Indeed, in mapping the contacts we found a correlation between the centrosome–cortex distance and the microtubule contact density. This density in turn modulates pulling force generator activity. We expanded our model of spindle rocking and predicted then experimentally validated that the oscillation onset position resists changes in cellular geometry and number of force generators. Consistent with final spindle position measurements, this new model accounts for a lower dependence on force generator dynamics and quantities than predicted by the previous model. Conclusion: The spindle position regulates the rapid increase in forces needed for anaphase oscillation and positioning through the spatial modulation of microtubule-cortex contacts. This regulation superimposes that of force generator processivity, putatively linked to the cell cycle. This novel control confers resistance to variations in zygote geometry and dynamics of cortical force generators. Interestingly, this robustness originates in cell mechanics rather than biochemical networks. Highlights • Microtubule contacts at the cortex concentrate in regions close to the centrosomes. • This regulates pulling forces and creates a positional switch on oscillation onset. • The onset position resists changes in embryo length and force generator dynamics. • The final centrosome position resists changes in generator quantities and dynamics.