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

Proceedings of the National Academy of Sciences of the United States of America
Masahiro HachisugaChikara Meno

Abstract

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.

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Citations

Aug 25, 2016·Molecular and Cellular Endocrinology·Patrick Y JayJames M Cheverud
Jul 20, 2017·Molecular Reproduction and Development·Kailun Hu, Yang Yu
May 18, 2018·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Erich RoesslerMaximilian Muenke
Jul 25, 2018·Congenital Anomalies·Hideyo OhuchiTetsuya Bando
Jul 28, 2016·Current Opinion in Lipidology·Anaïs BriotM Luisa Iruela-Arispe
Aug 23, 2018·Frontiers in Physiology·Jennifer A CourtneyHelen N Jones
Mar 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Xiaowei ZhengSergiu-Bogdan Catrina
Feb 13, 2021·Developmental Biology·Haruko NakanoAtsushi Nakano
Sep 10, 2021·Genesis : the Journal of Genetics and Development·Talita Z ChoudhuryVidu Garg

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