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MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice

Journal article
Authors Sanjiv Risal
Jingjing Zhang
D. Adhikari
X. M. Liu
Jingchen Shao
Kiran Busayavalasa
Zhaowei Tu
Z. J. Chen
P. Kaldis
Kui Liu
Published in Cell Discovery
Volume 3
ISSN 2056-5968
Publication year 2017
Published at Department of Chemistry and Molecular Biology
Language en
Links dx.doi.org/10.1038/celldisc.2016.52
Keywords anaphase, cell cycle, mitosis, MASTL, PP2A, primordial germ cells, protein phosphatase 2a, xenopus egg extracts, greatwall kinase, mitotic, progression, dna demethylation, mitosis, mouse, cycle, lineage, cdk1, Cell Biology, ates of america, v107, p12564
Subject categories Cell Biology

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 deleted Mastl in PGCs and found a significant loss of PGCs before the onset of meiosis in female PGCs. We further revealed that the deletion of Mastl in 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 of Mastl-null PGCs by 12.5 dpc. Moreover, the defect in mitotic progression observed in the Mastl-null PGCs was rescued by simultaneous deletion of Ppp2r1a (a 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.

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