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

Sanjiv Risal, JingJing Zhang, Deepak Adhikari, Xiaoman Liu, Jingchen Shao, Mengwen Hu, Kiran Busayavalasa, Zhaowei Tu, Zijiang Chen, Philipp Kaldis, Kui Liu

Research output: Contribution to journalArticleResearchpeer-review

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 (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.

Original languageEnglish
Article number16052
Number of pages14
JournalCell Discovery
Volume3
DOIs
Publication statusPublished - 7 Feb 2017

Keywords

  • anaphase
  • cell cycle
  • MASTL
  • mitosis
  • PP2A
  • primordial germ cells

Cite this

Risal, Sanjiv ; Zhang, JingJing ; Adhikari, Deepak ; Liu, Xiaoman ; Shao, Jingchen ; Hu, Mengwen ; Busayavalasa, Kiran ; Tu, Zhaowei ; Chen, Zijiang ; Kaldis, Philipp ; Liu, Kui. / MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice. In: Cell Discovery. 2017 ; Vol. 3.
@article{503b13b9d37e4406b328c712cf819d2c,
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 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.",
keywords = "anaphase, cell cycle, MASTL, mitosis, PP2A, primordial germ cells",
author = "Sanjiv Risal and JingJing Zhang and Deepak Adhikari and Xiaoman Liu and Jingchen Shao and Mengwen Hu and Kiran Busayavalasa and Zhaowei Tu and Zijiang Chen and Philipp Kaldis and Kui Liu",
year = "2017",
month = "2",
day = "7",
doi = "10.1038/celldisc.2016.52",
language = "English",
volume = "3",
journal = "Cell Discovery",
issn = "2056-5968",
publisher = "Springer",

}

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; Kaldis, Philipp; Liu, Kui.

In: Cell Discovery, Vol. 3, 16052, 07.02.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice

AU - Risal, Sanjiv

AU - Zhang, JingJing

AU - Adhikari, Deepak

AU - Liu, Xiaoman

AU - Shao, Jingchen

AU - Hu, Mengwen

AU - Busayavalasa, Kiran

AU - Tu, Zhaowei

AU - Chen, Zijiang

AU - Kaldis, Philipp

AU - Liu, Kui

PY - 2017/2/7

Y1 - 2017/2/7

N2 - 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.

AB - 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.

KW - anaphase

KW - cell cycle

KW - MASTL

KW - mitosis

KW - PP2A

KW - primordial germ cells

UR - http://www.scopus.com/inward/record.url?scp=85022225744&partnerID=8YFLogxK

U2 - 10.1038/celldisc.2016.52

DO - 10.1038/celldisc.2016.52

M3 - Article

VL - 3

JO - Cell Discovery

JF - Cell Discovery

SN - 2056-5968

M1 - 16052

ER -