Hyperglycemia impairs left–right axis formation and thereby disturbs heart morphogenesis in mouse embryos
| Autor: | Chikara Meno, Satomi Ikuta, Norio Wake, Keiko Kitajima, Tomoyuki Sumi, Masahiro Hachisuga, Kiyoko Kato, Shinya Oki |
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| Rok vydání: | 2015 |
| Předmět: |
Blood Glucose
Heart Defects Congenital Mesoderm medicine.medical_specialty Heart morphogenesis Time Factors Morphogenesis Notch signaling pathway Biology Mice Internal medicine medicine Animals Humans Phosphorylation Embryonic Stem Cells Body Patterning Multidisciplinary Receptors Notch PITX2 Lateral plate mesoderm Gene Expression Regulation Developmental Heart Embryonic stem cell Disease Models Animal Glucose HEK293 Cells medicine.anatomical_structure Endocrinology Hyperglycemia Microscopy Electron Scanning Female NODAL Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 112 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1504529112 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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