Computer simulations reveal mechanisms that organize nuclear dynein forces to separate centrosomes

Centrosome separation along the surface of the nucleus at the onset of mitosis is critical for bipolar spindle assembly. Dynein anchored on the nuclear envelope is known to be important for centrosome separation, but it is unclear how nuclear dynein forces are organized in an anisotropic manner to promote the movement of centrosomes away from each other. Here we use computational simulations of Caenorhabditis elegans embryos to address this fundamental question, testing three potential mechanisms by which nuclear dynein may act. First, our analysis shows that expansion of the nuclear volume per se does not generate nuclear dynein-driven separation forces. Second, we find that steric interactions between microtubules and centrosomes contribute to robust onset of nuclear dynein-mediated centrosome separation. Third, we find that the initial position of centrosomes, between the male pronucleus and cell cortex at the embryo posterior, is a key determinant in organizing microtubule aster asymmetry to power nuclear dynein-dependent separation. Overall our work reveals that accurate initial centrosome position, together with steric interactions, ensures proper anisotropic organization of nuclear dynein forces to separate centrosomes, thus ensuring robust bipolar spindle assembly.