Mammalian oocytes undergo highly asymmetric meiotic divisions, enabling the oocyte to retain the overwhelming majority of cytoplasmic contents for supporting embryogenesis. Inactivation of the major cell-cycle kinase, Cyclin-dependent kinase 1 (Cdk1), is critical for meiotic exit events including chromosome segregation and spindle midzone-directed furrowing of the overlying cortex. It is widely believed that by displacing the future midzone to an off-centre position, spindle migration before anaphase is the sole determinant of asymmetric oocyte division.
Here we simultaneously monitor chromosomes, spindles and membranes in live mouse oocytes at the highest temporal resolution to-date. For the first time, we detail the events occurring during anaphase of meiosis I. We find that anaphase-I lasts 25.4 min and is comprised of two unique phases; spindle elongation followed by spindle narrowing during both of which, chromosomes travel pole-wards. Unexpectedly, we discovered that the spindle migrates 8-9µm (12% of the oocyte diameter) after anaphase-onset, defining a new post-anaphase-onset phase of spindle migration. Strikingly, we found that the spindle migrated directly into the membrane. Spindle ingression into the membrane correlated strongly (R2=0.9884) with growth of a membrane protrusion over the leading spindle pole, eventually placing half of the spindle beyond the oocyte boundary before midzone-induced furrowing at the base of the protrusion. Intriguingly, Cdk1 inactivation not only triggered anaphase, it also induced spindle movement by generating a cytoplasmic force behind the spindle via a 47.3% increase in cytoplasmic F-actin polymerisation. Remarkably, we find that canonical pre-anaphase spindle migration is dispensable for normal asymmetric division provided that post-anaphase-onset spindle migration and protrusion remain intact.
Here we define a new model in which, Cdk1 inactivation induces an F-actin-dependent cytoplasmic force that propels the anaphase spindle into the membrane thereby inducing a protrusion, ultimately allowing half of the chromosomes to be ejected into the smallest possible polar body.