Hyperglycemia impairs left-right axis formation and thereby disturbs heart morphogenesis in mouse embryos

Masahiro Hachisuga, Shinya Oki, Keiko Kitajima, Satomi Ikuta, Tomoyuki Sumi, Kiyoko Kato, Norio Wake, Chikara Meno

研究成果: Contribution to journalArticle査読

14 被引用数 (Scopus)

抄録

Congenital heart defects with heterotaxia are associated with pregestational diabetes mellitus. To provide insight into the mechanisms underlying such diabetes-related heart defects, we examined the effects of high-glucose concentrations on formation of the left-right axis in mouse embryos. Expression of Pitx2, which plays a key role in left-right asymmetric morphogenesis and cardiac development, was lost in the left lateral plate mesoderm of embryos of diabetic dams. Embryos exposed to high-glucose concentrations in culture also failed to express Nodal and Pitx2 in the left lateral plate mesoderm. The distribution of phosphorylated Smad2 revealed that Nodal activity in the node was attenuated, accounting for the failure of left-right axis formation. Consistent with this notion, Notch signal-dependent expression of Nodal-related genes in the node was also down-regulated in association with a reduced level of Notch signaling, suggesting that high-glucose concentrations impede Notch signaling and thereby hinder establishment of the left-right axis required for heart morphogenesis.

本文言語英語
ページ(範囲)E5300-E5307
ジャーナルProceedings of the National Academy of Sciences of the United States of America
112
38
DOI
出版ステータス出版済み - 9 22 2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • General

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