RSK-MASTL Pathway Delays Meiotic Exit in Mouse Zygotes to Ensure Paternal Chromosome Stability

• Published in: Developmental cell Vol. 47; no. 3; pp. 363 - 376.e5
• Main Authors: Soeda, Shou, Yamada-Nomoto, Kaori, Michiue, Tatsuo, Ohsugi, Miho
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.11.2018
• Subjects: Animals; cell cycle; Chromatin Assembly and Disassembly; Chromosomal Instability; Chromosome Segregation; Cyclin B - metabolism; Female; fertilization; Male; Meiosis - physiology; meiotic exit; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; mouse early development; Oocytes - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Ribosomal Protein S6 Kinases - genetics; Ribosomal Protein S6 Kinases - metabolism; signaling pathway; Spermatozoa - metabolism; Spermatozoa - physiology; Xenopus laevis; Zygote - metabolism; Zygote - physiology; signaling pathway; fertilization; meiotic exit; cell cycle; mouse early development
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2018.09.011

During vertebrate fertilization, sperm chromatin remodeling occurs concomitantly with maternal chromosome segregation at anaphase II, leading to simultaneous formation of two pronuclei. In mammals, these processes take much longer than in other vertebrates. Here, we explore the molecular basis and physiological importance of this mammalian-specific temporal regulation using mouse oocytes. We demonstrate the involvement of protein phosphatase in temporal regulation. Early onset of pronuclear formation causes paternal-biased abnormalities in pronuclear morphology and chromosome segregation at the first mitosis. After oocyte activation, CDK1-MASTL-ENSA, a protein phosphatase 2A-suppressive pathway, remains active despite the absence of cyclin B and contributes to delayed pronuclear formation. Sustained activation of MASTL involves ribosomal S6 kinase (RSK)-mediated phosphorylation of Thr297, which is conserved only among mammalian MASTLs. Our findings reveal the role of RSK in mouse oocytes, showing that the RSK-MASTL pathway allows mammalian-specific prolonged meiotic exit and ensures the faithful conversion from sperm to paternal pronuclei. [Display omitted] •Delayed meiotic exit ensures paternal chromosome stability in mouse zygotes•Sustained activation of MASTL contributes to delayed onset of pronuclear formation•RSK phosphorylates MASTL on Thr297 and sustains its activity after CDK1 inactivation•RSK-MASTL pathway is a mammalian-specific temporal regulator of oocyte meiotic exit Soeda et al. demonstrate that sustained activation of MASTL by RSK-mediated phosphorylation of Thr297 delays meiotic exit and provides sufficient time for sperm chromatin remodeling in mouse zygotes. The mammalian specific MASTL-RSK pathway explains the difference in the timing of oocyte meiotic exit between mouse and Xenopus.