Short Report

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

Valerie Tilston^1,2 , Stephen S Taylor¹ and David Perera¹

¹Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK

²MRC Centre for Drug Safety Science, Department of Pharmacology & Therapeutics, The University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, UK

author email corresponding author email

BMC Research Notes 2009, 2:190doi:10.1186/1756-0500-2-190

Published:	23 September 2009

Abstract

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.