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

Risal, Sanjiv ; Zhang, Jingjing ; Adhikari, Deepak ; Liu, Xiaoman ; Shao, Jingchen ; Hu, Mengwen ; Busayavalasa, Kiran ; Tu, Zhaowei ; Chen, Zijiang and Kaldis, Philipp LU orcid , et al. (2017) In Cell Discovery 3.
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... (More)

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 (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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
anaphase, cell cycle, MASTL, mitosis, PP2A, primordial germ cells
in
Cell Discovery
volume
3
article number
16052
publisher
Nature Publishing Group
external identifiers
  • scopus:85022225744
ISSN
2058-7716
DOI
10.1038/celldisc.2016.52
language
English
LU publication?
no
id
fe1980bf-98ff-4716-9b93-37f3714228a1
date added to LUP
2019-09-18 10:14:48
date last changed
2022-04-26 05:43:32
@article{fe1980bf-98ff-4716-9b93-37f3714228a1,
  abstract     = {{<p>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 (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.</p>}},
  author       = {{Risal, Sanjiv and Zhang, Jingjing and Adhikari, Deepak and Liu, Xiaoman and Shao, Jingchen and Hu, Mengwen and Busayavalasa, Kiran and Tu, Zhaowei and Chen, Zijiang and Kaldis, Philipp and Liu, Kui}},
  issn         = {{2058-7716}},
  keywords     = {{anaphase; cell cycle; MASTL; mitosis; PP2A; primordial germ cells}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Cell Discovery}},
  title        = {{MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice}},
  url          = {{http://dx.doi.org/10.1038/celldisc.2016.52}},
  doi          = {{10.1038/celldisc.2016.52}},
  volume       = {{3}},
  year         = {{2017}},
}