論文

査読有り 国際誌
2017年10月15日

Klf5 maintains the balance of primitive endoderm versus epiblast specification during mouse embryonic development by suppression of Fgf4.

Development (Cambridge, England)
  • Takuya Azami
  • ,
  • Tsuyoshi Waku
  • ,
  • Ken Matsumoto
  • ,
  • Hyojung Jeon
  • ,
  • Masafumi Muratani
  • ,
  • Akihiro Kawashima
  • ,
  • Jun Yanagisawa
  • ,
  • Ichiro Manabe
  • ,
  • Ryozo Nagai
  • ,
  • Tilo Kunath
  • ,
  • Tomonori Nakamura
  • ,
  • Kazuki Kurimoto
  • ,
  • Mitinori Saitou
  • ,
  • Satoru Takahashi
  • ,
  • Masatsugu Ema

144
20
開始ページ
3706
終了ページ
3718
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1242/dev.150755

The inner cell mass of the mouse blastocyst gives rise to the pluripotent epiblast (EPI), which forms the embryo proper, and the primitive endoderm (PrE), which forms extra-embryonic yolk sac tissues. All inner cells coexpress lineage markers such as Nanog and Gata6 at embryonic day (E) 3.25, and the EPI and PrE precursor cells eventually segregate to exclusively express Nanog and Gata6, respectively. Fibroblast growth factor (FGF)-extracellular signal-regulated kinase (ERK) signalling is involved in segregation of the EPI and PrE lineages; however, the mechanism involved in Fgf4 regulation is poorly understood. Here, we identified Klf5 as an upstream repressor of Fgf4Fgf4 was markedly upregulated in Klf5 knockout (KO) embryos at E3.0, and was downregulated in embryos overexpressing Klf5 Furthermore, Klf5 KO and overexpressing blastocysts showed skewed lineage specification phenotypes, similar to FGF4-treated preimplantation embryos and Fgf4 KO embryos, respectively. Inhibitors of the FGF receptor (Fgfr) and ERK pathways reversed the skewed lineage specification of Klf5 KO blastocysts. These data demonstrate that Klf5 suppresses Fgf4-Fgfr-ERK signalling, thus preventing precocious activation of the PrE specification programme.

リンク情報
DOI
https://doi.org/10.1242/dev.150755
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28870993
URL
http://europepmc.org/abstract/med/28870993
ID情報
  • DOI : 10.1242/dev.150755
  • ORCIDのPut Code : 37563341
  • PubMed ID : 28870993

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