Loss of the maternal imprint in Dnmt3Lmat-/- mice leads to a differentiation defect in the extraembryonic tissue

Takahiro Arima, Kenichiro Hata, Satoshi Tanaka, Maki Kusumi, En Li, Kiyoko Kato, Kunio Shiota, Hiroyuki Sasaki, Norio Wake

研究成果: Article査読

74 被引用数 (Scopus)

抄録

DNA methylation of the genome is essential for mammalian development and plays crucial roles in a variety of biological processes including genomic imprinting. Although the DNA methyltransferase 3-like (Dnmt3L) protein lacks DNA methylase activity, it is thought to establish the maternal imprint in combination with the functional DNA methyltransferases. Oogenesis apparently proceeds normally in female mice homozygous for a targeted deletion of Dnmt3L, but their heterozygous offspring (Dnmt3Lmat-/-) die before midgestation due to an imprinting defect. In this study, we show that Dnmt3L is required for the establishment of maternal methylation imprints both in the embryos and the placentae and that the placentae of these embryos develop abnormally. There is a defect in the formation of the labyrinth, reduced formation of the spongiotrophoblast layer, excess trophoblast giant cells and insufficient attachment between the chorion layer and the ectoplacental cone. In addition, we demonstrate arrest of proliferation of the extraembryonic tissue without apoptosis in vivo and a disturbance of the cell fate of Dnmt3Lmat-/- trophoblastic stem cells in vitro. Furthermore, we report that DNA methylation during oogenesis is essential for the establishment of imprinting Mash2. These findings provide evidence that not only is DNA methylation required for the appropriate maternal imprint in the placenta but that the appropriate imprint is absolutely required for vertebrate placentation.

本文言語English
ページ(範囲)361-373
ページ数13
ジャーナルDevelopmental Biology
297
2
DOI
出版ステータスPublished - 2006 9 15
外部発表はい

ASJC Scopus subject areas

  • 発生生物学

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