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Updated: Jun 26, 2026
Meiotic Spindle Assessment in Mouse Oocytes by siRNA-mediated Silencing
Published on: October 11, 2015
Preimplantation mouse embryos depend on inhibitory phosphorylation of separase to prevent chromosome missegregation
Xingxu Huang1, Claudia V Andreu-Vieyra, Meizhi Wang
1Model Animal Research Center, Nanjing University, Pukou District, Nanjing, China. huangxx@nicemice.cn
Abstract:
Separase is a critical protease that catalyzes the cleavage of sister chromatid cohesins to allow the separation of sister chromatids in the anaphase. Its activity must be inhibited prior to the onset of the anaphase. Two inhibitory mechanisms exist in vertebrates that block the protease activity. One mechanism is through binding and inhibition by securin, and another is phosphorylation on Ser1126 (in humans [Ser1121 in mice]). These two mechanisms are largely redundant. However, phosphorylation on Ser1121 is critical for the prevention of premature sister separation in embryonic germ cells. As a result, Ser1121-to-Ala mutation leads to depletion of germ cells in development and subsequently to infertility in mice. Here, we report that the same mutation also causes embryogenesis failure between the 8- and 16-cell stages in mice. Our results indicate a critical role of separase phosphorylation in germ cell development as well as in early embryogenesis. Thus, deregulation of separase may be a significant contributor to infertility in humans.
Insights
Separase phosphorylation is vital for preventing premature sister chromatid separation. A mutation in separase phosphorylation causes germ cell depletion, infertility, and early embryogenesis failure in mice.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Separase protease activity is essential for sister chromatid separation during anaphase.
- Inhibitory mechanisms, including securin binding and phosphorylation, regulate separase.
- Phosphorylation on Ser1121 in mice is crucial for germ cell development.
Purpose of the Study:
- To investigate the role of separase phosphorylation in early embryogenesis.
- To determine the consequences of a Ser1121-to-Ala mutation in mouse separase.
Main Methods:
- Generation of mice with a Ser1121-to-Ala mutation in separase.
- Analysis of germ cell development and embryogenesis in mutant mice.
Main Results:
- The Ser1121-to-Ala mutation leads to depletion of germ cells and infertility.
- Mutant mice exhibit embryogenesis failure between the 8- and 16-cell stages.
- Separase phosphorylation is critical for both germ cell development and early embryogenesis.
Conclusions:
- Separase phosphorylation plays a critical role in mammalian development.
- Deregulation of separase activity may contribute to human infertility.
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