論文

査読有り 国際誌
2017年11月2日

Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice.

The EMBO journal
  • Hidetaka Miyauchi
  • ,
  • Hiroshi Ohta
  • ,
  • So Nagaoka
  • ,
  • Fumio Nakaki
  • ,
  • Kotaro Sasaki
  • ,
  • Katsuhiko Hayashi
  • ,
  • Yukihiro Yabuta
  • ,
  • Tomonori Nakamura
  • ,
  • Takuya Yamamoto
  • ,
  • Mitinori Saitou

36
21
開始ページ
3100
終了ページ
3119
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.15252/embj.201796875

The mechanism for sex determination in mammalian germ cells remains unclear. Here, we reconstitute the female sex determination in mouse germ cells in vitro under a defined condition without the use of gonadal somatic cells. We show that retinoic acid (RA) and its key effector, STRA8, are not sufficient to induce the female germ-cell fate. In contrast, bone morphogenetic protein (BMP) and RA synergistically induce primordial germ cells (PGCs)/PGC-like cells (PGCLCs) derived from embryonic stem cells (ESCs) into fetal primary oocytes. The induction is characterized by entry into the meiotic prophase, occurs synchronously and recapitulates cytological and transcriptome progression in vivo faithfully. Importantly, the female germ-cell induction necessitates a proper cellular competence-most typically, DNA demethylation of relevant genes-which is observed in appropriately propagated PGCs/PGCLCs, but not in PGCs/PGCLCs immediately after induction. This provides an explanation for the differential function of BMP signaling between PGC specification and female germ-cell induction. Our findings represent a framework for a comprehensive delineation of the sex-determination pathway in mammalian germ cells, including humans.

リンク情報
DOI
https://doi.org/10.15252/embj.201796875
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28928204
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666620
URL
http://europepmc.org/abstract/med/28928204
ID情報
  • DOI : 10.15252/embj.201796875
  • ORCIDのPut Code : 37563339
  • PubMed ID : 28928204
  • PubMed Central 記事ID : PMC5666620

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