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Background  Bub1 is a component of the spindle assembly checkpoint, a surveillance mechanism that maintains chromosome stability during M-phase. Bub1 is essential during the early stages of embryogenesis, with homozygous  BUB1 -null mice dying shortly after day E3.5. Bub1 is also required later during embryogenesis; inactivation of  BUB1  on day E10.5 appears to rapidly block all further development. However, the mechanism(s) responsible for this phenotype remain unclear.    Findings  Here we show that inactivating  BUB1  on day E10.5 stalls embryogenesis within 48 hours. This is accompanied by a global shutdown of proliferation, widespread apoptosis and haemorrhaging.    Conclusion  Our results suggest that Bub1 is required throughout the developing embryo for cellular proliferation. Therefore, Bub1 has been shown to be essential in all scenarios analyzed thus far in mice: proliferation of cultured fibroblasts, spermatogenesis, oogenesis and both early and late embryonic development. This likely reflects the fact that Bub1 has dual functions during mitosis, being required for both SAC function and chromosome alignment.

Inactivating the spindle checkpoint kinase Bub1 during embryonic development results in a global shutdown of proliferation