title: MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice.
abstract: In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75-8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs. We generated a mouse model where we specifically deletedMastlin PGCs and found a significant loss of PGCs before the onset of meiosis in female PGCs. We further revealed that the deletion ofMastlin PGCs did not prevent mitotic entry, but led to a failure of the cells to proceed beyond metaphase-like stage, indicating that MASTL-mediated molecular events are indispensable for anaphase entry in PGCs. These mitotic defects further led to the death ofMastl-null PGCs by 12.5 dpc. Moreover, the defect in mitotic progression observed in theMastl-null PGCs was rescued by simultaneous deletion ofPpp2r1a(α subunit of PP2A). Thus, our results demonstrate that MASTL, PP2A, and therefore regulated phosphatase activity have a fundamental role in establishing female germ cell population in gonads by controlling PGC proliferation during embryogenesis.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , Gothenburg, Sweden.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Risal
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , Gothenburg, Sweden.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Monash Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University , Melbourne, Victoria, Australia.
authors.forename: Deepak
authors.initials: D
authors.lastname: Adhikari
authors.affiliation: The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education , Jinan, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , Gothenburg, Sweden.
authors.forename: Jingchen
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , Gothenburg, Sweden.
authors.forename: Mengwen
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , Gothenburg, Sweden.
authors.forename: Kiran
authors.initials: K
authors.lastname: Busayavalasa
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , Gothenburg, Sweden.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Tu
authors.affiliation: The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education , Jinan, China.
authors.forename: Zijiang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Molecular and Cell Biology (IMCB), ASTAR (Agency for Science, Technology and Research), Singapore, Republic of Singapore; Department of Biochemistry, National University of Singapore (NUS), Singapore, Republic of Singapore.
authors.forename: Philipp
authors.identifier: 0000-0002-7247-7591
authors.initials: P
authors.lastname: Kaldis
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden; The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
keywords: MASTL; PP2A; anaphase; cell cycle; mitosis; primordial germ cells