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Inhibition of c-mos protein kinase blocks mouse zygotes at the pronuclei stage
X Zhao1, B Singh, R B Arlinghaus
1Department of Medicine, Stanford University School of Medicine, California 94305.
Abstract:
The c-mos gene product is required for activation of the maturation-promoting factor (MPF) during oocyte maturation. The c-mos protein also acts as a cytostatic factor which is responsible for meiotic metaphase arrest of vertebrate eggs via stabilization of MPF. Here we show that mouse zygotes contain the c-mos protein. Introduction of a kinase-inhibitory anti-mos antibody into mouse zygotes 12 h after fertilization prevented the first cleavage of zygotes at the pronuclei stage. A second anti-mos antibody, known to allow the mos kinase to function, did not interfere with the formation of two-cell embryos. In addition to its known role in MPF activation in oocyte maturation and meiotic metaphase arrest, our findings indicate that the c-mos protein kinase is also required for completion of pronuclei breakdown following fertilization of mouse eggs.
Insights
The c-mos protein is essential for mouse zygote development after fertilization. Inhibiting its kinase activity prevents the first cell division, highlighting its role beyond oocyte maturation.
Area of Science:
- Molecular and Developmental Biology
- Cell Cycle Regulation
Background:
- The c-mos proto-oncogene product is crucial for initiating oocyte maturation by activating maturation-promoting factor (MPF).
- c-mos protein functions as a cytostatic factor, maintaining meiotic metaphase arrest through MPF stabilization in vertebrate eggs.
Purpose of the Study:
- To investigate the presence and function of c-mos protein in mouse zygotes post-fertilization.
- To determine if c-mos protein kinase activity is required for early embryonic development, specifically pronuclei breakdown and first cleavage.
Main Methods:
- Microinjection of kinase-inhibitory and non-inhibitory anti-mos antibodies into fertilized mouse zygotes.
- Observation and assessment of zygote cleavage and embryonic development at the pronuclei and two-cell stages.
- Timing of antibody introduction at 12 hours post-fertilization.
Main Results:
- Mouse zygotes were confirmed to contain the c-mos protein.
- Introduction of a kinase-inhibitory anti-mos antibody blocked the first zygotic cleavage at the pronuclei stage.
- A control antibody, allowing mos kinase function, did not impede the formation of two-cell embryos.
Conclusions:
- The c-mos protein kinase plays a vital role in mouse zygotes, extending beyond its established functions in oocyte maturation.
- c-mos protein kinase activity is indispensable for the completion of pronuclei breakdown, a critical event following fertilization.
- These findings reveal a novel requirement for c-mos in the transition from zygote to early embryonic development.
