A persistent intracellular bridge and cell cycle misregulation enable polar body cell divisions and tumor formation in Mos-deficient eggs.

Mammalian female meiosis is uniquely regulated to produce a developmentally competent egg capable of supporting embryogenesis. During meiosis I, homologous chromosomes segregate, with half extruded into the first polar body. The egg then arrests at metaphase II and only resumes meiosis and extrudes the second polar body following fertilization. The MOS/MAPK signaling pathway is important for maintaining the metaphase II arrest; in mos (-/-) mutants, a subset of eggs undergo spontaneous parthenogenetic activation and exhibit additional abnormal cell divisions. To further understand the cell cycle mis-regulation in activated mos (-/-) eggs, we used time-lapse microscopy to monitor the abnormal divisions. We discovered that, following parthenogenetic activation, the first polar body can assemble a spindle, segregate chromosomes, and divide with timings similar to anaphase II onset in the egg. This behavior contrasts with wildtype polar bodies, which do not divide and are typically degenerated. We demonstrate that mos (-/-) eggs and polar bodies can exchange cytoplasm at the time of meiosis II spindle assembly, likely allowing the transfer of cell cycle regulators between the two compartments. Further inspection revealed that mos (-/-) eggs have defective meiotic midbody assembly with most eggs lacking a cap structure, which is needed to separate the two compartments. We report that polar bodies of mos (-/-) eggs can re-enter the cell cycle and undergo additional aberrant divisions. These findings identify MOS as a critical regulator of meiotic midbody formation and uncover a novel consequence of disrupted MOS/MAPK signaling: the potential for polar bodies to become mitotically active and contribute to tumor formation.