| Project/Area Number |
12680724
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Developmental biology
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| Research Institution | Okazaki National Research Institutes |
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Principal Investigator |
HAMADA Yoshio Natiomal Institute of Basic Biology.Tissue and Cell Culture Laboratory.Research Associate, 基礎生物学研究所, 助手 (10132739)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Satoshi The University of Tokyo.Animal Resource Sciences/Veterinary Medical Sciences.Laboratory of Cellular Biochemistry.Associate Professor, 大学院農学・生命科学研究科, 助教授 (90242164)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Notch2 signaling pathway / vasculogenesis / labyrinthine trophoblast / tetraploid rescue / Notch2 / 血管内皮 / キムラ解析 |
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| Research Abstract |
The Notch gene family encodes large Tran membrane receptors that are components of an evolutionarily conserved intercellular signaling mechanism. Mutation in the ankyrin repeats of mouse Notch2 results in embryonic lethality by embryonic day 11.5 (E11.5), indicating that Notch2 plays an essential role in post implantation development in mice. Development of the mutant embryos in whole embryo culture indicated that the lethality was likely caused by defects in the extra embryonic tissues. Histological examination and in situ hybridization analysis revealed inadequate vasculogenesis in the labyrinth layer of the mutant placenta with apparently normal differentiation of secondary giant cells and spongiotrophoblast cells. The lethality was delayed by production of chimeric concept uses with tetraploid (4N) wild type embryos. These results collectively suggest that the fatal defect in Notch2 mutants is in labyrinthine trophoblast cells. Mutant cells, however, contributed to all layers of E12.5 chimeric placentas, indicating that the mutation did not affect the cell fate decision or the survival of trophoblast subtypes. Rather, it compromised physiological functions of labyrinthine trophoblast cells, probably including cell-cell interactions with allantoic mesenchyme. Furthermore, the 4N-rescued mutant embryos did not survive beyond E12.5, at which time they exhibited an anemic phenotype and insufficient development of the umbilical cord. Thus, Notch2 is not cell autonomously required for the early cell fate determination of labyrinthine trophoblast and allantoic mesodermal cells, but plays an indispensable role in the further formation of a functional labyrinth layer and the umbilical cord.
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