TY - JOUR
T1 - Spindle assembly checkpoint regulates mitotic cell cycle progression during preimplantation embryo development
AU - Wei, Yanchang
AU - Multi, Saima
AU - Yang, Cai-Rong
AU - Ma, Junyu
AU - Zhang, Qing Hua
AU - Wang, Zhen Bo
AU - Li, Mo
AU - Wei, Liang
AU - Ge, Zhao Jia
AU - Zhang, Chun Hui
AU - Ouyang, Ying-Chun
AU - Hou, Yi
AU - Schatten, Heide
AU - Sun, Qing-Yuan
PY - 2011
Y1 - 2011
N2 - Errors in chromosome segregation or distribution may result in aneuploid embryo formation, which causes implantation failure, spontaneous abortion, genetic diseases, or embryo death. Embryonic aneuploidy occurs when chromosome aberrations are present in gametes or early embryos. To date, it is still unclear whether the spindle assembly checkpoint (SAC) is required for the regulation of mitotic cell cycle progression to ensure mitotic fidelity during preimplantation development. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of SAC components (Bub3, BubR1 and Mad2) in mouse preimplantation embryos. Our data showed that overexpressed SAC components inhibited metaphase-anaphase transition by preventing sister chromatid segregation. Deletion of SAC components by RNAi accelerated the metaphase-anaphase transition during the first cleavage and caused micronuclei formation, chromosome misalignment and aneuploidy, which caused decreased implantation and delayed development. Furthermore, in the presence of the spindle-depolymerizing drug nocodazole, SAC depleted embryos failed to arrest at metaphase. Our results suggest that SAC is essential for the regulation of mitotic cell cycle progression in cleavage stage mouse embryos.
AB - Errors in chromosome segregation or distribution may result in aneuploid embryo formation, which causes implantation failure, spontaneous abortion, genetic diseases, or embryo death. Embryonic aneuploidy occurs when chromosome aberrations are present in gametes or early embryos. To date, it is still unclear whether the spindle assembly checkpoint (SAC) is required for the regulation of mitotic cell cycle progression to ensure mitotic fidelity during preimplantation development. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of SAC components (Bub3, BubR1 and Mad2) in mouse preimplantation embryos. Our data showed that overexpressed SAC components inhibited metaphase-anaphase transition by preventing sister chromatid segregation. Deletion of SAC components by RNAi accelerated the metaphase-anaphase transition during the first cleavage and caused micronuclei formation, chromosome misalignment and aneuploidy, which caused decreased implantation and delayed development. Furthermore, in the presence of the spindle-depolymerizing drug nocodazole, SAC depleted embryos failed to arrest at metaphase. Our results suggest that SAC is essential for the regulation of mitotic cell cycle progression in cleavage stage mouse embryos.
UR - http://www.scopus.com/inward/record.url?scp=79959617241&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0021557
DO - 10.1371/journal.pone.0021557
M3 - Article
C2 - 21720555
AN - SCOPUS:79959617241
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e21557
ER -