Pdgfrα functions in endothelial-derived cells to regulate neural crest cells and the development of the great arteries
| Autor: | Young Kuk Cho, Haig Aghajanian, Rajan Jain, Li Li, Qiaohong Wang, Karl Degenhardt, Nicholas W. Rizer |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male congenital hereditary and neonatal diseases and abnormalities Receptor Platelet-Derived Growth Factor alpha Genotype Neuroscience (miscellaneous) Medicine (miscellaneous) Persistent truncus arteriosus lcsh:Medicine PDGFRA Biology General Biochemistry Genetics and Molecular Biology Mesoderm 03 medical and health sciences Neural crest Mice Immunology and Microbiology (miscellaneous) Double outlet right ventricle medicine.artery Conotruncal defect medicine lcsh:Pathology Animals Endothelium Outflow tract Cardiogenesis lcsh:R Endothelial Cells Anatomy Arteries medicine.disease Embryo Mammalian Aorticopulmonary septum 030104 developmental biology Great arteries Pulmonary artery cardiovascular system Pdgfrα Female Endothelium Vascular Gene Deletion lcsh:RB1-214 Research Article |
| Zdroj: | Disease Models & Mechanisms Disease Models & Mechanisms, Vol 10, Iss 9, Pp 1101-1108 (2017) |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | Originating as a single vessel emerging from the embryonic heart, the truncus arteriosus must septate and remodel into the aorta and pulmonary artery to support postnatal life. Defective remodeling or septation leads to abnormalities collectively known as conotruncal defects, which are associated with significant mortality and morbidity. Multiple populations of cells must interact to coordinate outflow tract remodeling, and the cardiac neural crest has emerged as particularly important during this process. Abnormalities in the cardiac neural crest have been implicated in the pathogenesis of multiple conotruncal defects, including persistent truncus arteriosus, double outlet right ventricle and tetralogy of Fallot. However, the role of the neural crest in the pathogenesis of another conotruncal abnormality, transposition of the great arteries, is less well understood. In this report, we demonstrate an unexpected role of Pdgfra in endothelial cells and their derivatives during outflow tract development. Loss of Pdgfra in endothelium and endothelial-derived cells results in double outlet right ventricle and transposition of the great arteries. Our data suggest that loss of Pdgfra in endothelial-derived mesenchyme in the outflow tract endocardial cushions leads to a secondary defect in neural crest migration during development. Summary: Loss of Pdgfrα in endothelial-derived mesenchyme results in defective neural crest behavior and is associated with conotruncal defects including, surprisingly, transposition of the great arteries. |
| Databáze: | OpenAIRE |
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