Meiotic divisions in oocytes are extremely asymmetric and require pre- and post-anaphase-onset phases of spindle migration. The latter induces membrane protrusion that is moulded around the spindle thereby reducing cytoplasmic loss. Here, we find that depleting the NAD biosynthetic enzyme, nicotinamide phosphoribosyl-transferase (Nampt), in mouse oocytes results in markedly longer spindles and compromises asymmetry. By analysing spindle speed in live oocytes, we identify a striking and transient acceleration after anaphase-onset that is severely blunted following Nampt-depletion. Slow-moving midzones of elongated spindles induce cortical furrowing deep within the oocyte before protrusions can form, altogether resulting in larger oocyte fragments being cleaved off. Additionally, we find that Nampt-depletion lowers NAD and ATP levels and that reducing NAD using small molecule Nampt inhibitors also compromises asymmetry. These data show that rapid midzone displacement is critical for extreme asymmetry by delaying furrowing to enable protrusions to form and link metabolic status to asymmetric division.

卵母细胞中的减数分裂非常不对称，并且需要纺锤体迁移的后期和后期开始阶段。后者诱导在纺锤周围模制的膜突出，从而减少细胞质损失。在这里，我们发现消耗NAD生物合成酶烟酰胺磷酸核糖基转移酶（Nampt），在小鼠卵母细胞中导致明显更长的纺锤体并损害不对称性。通过分析活卵母细胞的纺锤速度，我们确定了后期发作后的突触和瞬态加速度，其在Nampt耗竭后严重变钝。细长纺锤体的缓慢移动的中间区域会在卵母细胞深处形成皮质沟，然后才能形成突起，从而导致更大的卵母细胞碎片被切除。此外，我们发现Nampt耗竭会降低NAD和ATP的水平，使用小分子Nampt抑制剂降低NAD也会损害不对称性。这些数据表明，通过延迟犁沟使突起形成并将新陈代谢状态与不对称分裂相关联，快速的中区移位对于极端不对称至关重要。