Notch2 is required for formation of the placental circulatory system, but not for cell-type specification in the developing mouse placenta

Yoshio Hamada, Takeshi Hiroe, Yuko Suzuki, Mayumi Oda, Yoshihide Tsujimoto, John R. Coleman, Satoshi Tanaka

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

We have previously reported that a mutation in the ankyrin repeats of mouse Notch2 results in embryonic lethality by embryonic day 11.5 (E11.5), showing developmental retardation at E10.5. This indicated that Notch2 plays an essential role in postimplantation development in mice. Here, we demonstrate that whole embryo culture can circumvent developmental retardation of Notch2 mutant embryos for up to 1 day, suggesting that the lethality was primarily caused by extraembryonic defects. Histological examinations revealed delayed entry of maternal blood into the mutant placenta and poor blood sinus formation at later stages. Notch2-expressing cells appeared around maternal blood sinuses. Specification of trophoblast subtypes appeared not to be drastically disturbed and expression of presumptive downstream genes of Notch2 signaling was not altered by the Notch2 mutation. Thus, in the developing mouse placenta, Notch2 is unlikely to be involved in cell fate decisions, but rather participates in formation of maternal blood sinuses. In aggregation chimeras with wild-type tetraploid embryos, the mutant embryos developed normally until E12.5, but died before E13.5. The chimeric placentas showed a restored maternal blood sinus formation when compared with the mutant placentas, but not at the level of wild-type diploid placentas. Therefore, it was concluded that the mutant suffers from defects in maternal blood sinus formation. Thus, Notch2 is not cell autonomously required for the early cell fate determination of subtypes of trophoblast cells, but plays an indispensable role in the formation of maternal blood sinuses in the developing mouse placenta.

Original languageEnglish
Pages (from-to)268-278
Number of pages11
JournalDifferentiation
Volume75
Issue number3
DOIs
Publication statusPublished - 2007 Mar

Keywords

  • Cell-cell interaction
  • Maternal blood sinus
  • Notch2
  • Tetraploid chimera
  • Trophoblast differentiation
  • Vasculogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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