Cdk1 inactivation induces post-anaphase-onset spindle migration and membrane protrusion required for extreme...

Area of Science:

• Cell Biology
• Developmental Biology
• Reproductive Biology

Background:

• Female meiosis is characterized by highly asymmetric cell divisions, yielding a large oocyte and small polar bodies (PBs).
• In mouse oocytes, the spindle repositions to the cell cortex before meiosis I anaphase, a process presumed to solely ensure asymmetry.
• The contribution of post-anaphase events to asymmetric polar body extrusion remains largely unexplored.

Purpose of the Study:

• To investigate the role of post-anaphase events in asymmetric polar body extrusion during mouse oocyte meiosis.
• To elucidate the mechanisms underlying cell-cycle-triggered spindle displacement and its impact on meiotic division asymmetry.

Main Methods:

• Inactivation of cyclin-dependent kinase 1 (Cdk1) to induce anaphase.
• Live imaging and microscopy to observe spindle dynamics and F-actin polymerization.
• Perturbation experiments to assess the necessity of pre- and post-anaphase spindle migration for asymmetry.

Main Results:

• Inactivation of Cdk1 triggers F-actin polymerization, propelling the spindle towards the cortex during anaphase.
• Post-anaphase spindle migration is essential for oocyte protrusion and asymmetric polar body extrusion.
• Failure of post-anaphase migration severely compromises asymmetry, even if pre-anaphase migration is intact.
• Post-anaphase migration can rescue asymmetry when pre-anaphase migration fails.

Conclusions:

• A critical cell-cycle-triggered phase of spindle displacement occurs after anaphase onset, driving cortical protrusion.
• This post-anaphase spindle migration is necessary for achieving extreme asymmetry in mouse oocytes.
• These findings reveal a novel pathway for maximizing unequal cell division during oogenesis.