Differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart development
Abstract Background The embryonic day E10–13 period of mouse heart development is characterized by robust cardiomyocyte proliferation that creates the compact zone of thickened ventricular wall myocardium. This process is initiated by the formation of the epicardium on the outer heart surface, which...
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doaj-e16c85d214124d9288a731536a3a9cc42020-11-25T02:10:01ZengBMCBMC Developmental Biology1471-213X2019-03-011911810.1186/s12861-019-0186-8Differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart developmentKai Wang0Hua Shen1Peiheng Gan2Susana Cavallero3S. Ram Kumar4Ching-Ling Lien5Henry M. Sucov6Department of Cardiovascular Surgery, the First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern CaliforniaDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern CaliforniaDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern CaliforniaDepartment of Surgery, Keck School of Medicine, University of Southern CaliforniaSaban Research Institute, Children’s Hospital Los AngelesDepartment of Regenerative Medicine and Cell Biology, Medical University of South CarolinaAbstract Background The embryonic day E10–13 period of mouse heart development is characterized by robust cardiomyocyte proliferation that creates the compact zone of thickened ventricular wall myocardium. This process is initiated by the formation of the epicardium on the outer heart surface, which releases insulin-like growth factor 2 (IGF2) as the primary cardiomyocyte mitogen. Two receptors mediate IGF2 signaling, the IGF1R and the insulin receptor (INSR). Results In this study, we addressed the relative roles of the two IGF2 receptors in mouse heart development. We find that both receptors are expressed in the mouse heart during the E10–13 period, although IGF1R is much more prominently activated by IGF2 than INSR. Genetic manipulation indicates that only Igf1r is required for embryonic ventricular wall morphogenesis. INSR is not hyperactivated in the absence of IGF1R, and INSR does not compensate functionally for IGF1R in the absence of the latter. Conclusions These results define the molecular components that are responsible for a major burst of cardiomyocyte proliferation during heart development. These results may also be relevant to understanding the efficiency of regeneration of the mammalian heart after neonatal and adult injury.http://link.springer.com/article/10.1186/s12861-019-0186-8Heart developmentEpicardiumIGF2IGF1RInsulin receptorCardiomyocyte proliferation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kai Wang Hua Shen Peiheng Gan Susana Cavallero S. Ram Kumar Ching-Ling Lien Henry M. Sucov |
spellingShingle |
Kai Wang Hua Shen Peiheng Gan Susana Cavallero S. Ram Kumar Ching-Ling Lien Henry M. Sucov Differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart development BMC Developmental Biology Heart development Epicardium IGF2 IGF1R Insulin receptor Cardiomyocyte proliferation |
author_facet |
Kai Wang Hua Shen Peiheng Gan Susana Cavallero S. Ram Kumar Ching-Ling Lien Henry M. Sucov |
author_sort |
Kai Wang |
title |
Differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart development |
title_short |
Differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart development |
title_full |
Differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart development |
title_fullStr |
Differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart development |
title_full_unstemmed |
Differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart development |
title_sort |
differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart development |
publisher |
BMC |
series |
BMC Developmental Biology |
issn |
1471-213X |
publishDate |
2019-03-01 |
description |
Abstract Background The embryonic day E10–13 period of mouse heart development is characterized by robust cardiomyocyte proliferation that creates the compact zone of thickened ventricular wall myocardium. This process is initiated by the formation of the epicardium on the outer heart surface, which releases insulin-like growth factor 2 (IGF2) as the primary cardiomyocyte mitogen. Two receptors mediate IGF2 signaling, the IGF1R and the insulin receptor (INSR). Results In this study, we addressed the relative roles of the two IGF2 receptors in mouse heart development. We find that both receptors are expressed in the mouse heart during the E10–13 period, although IGF1R is much more prominently activated by IGF2 than INSR. Genetic manipulation indicates that only Igf1r is required for embryonic ventricular wall morphogenesis. INSR is not hyperactivated in the absence of IGF1R, and INSR does not compensate functionally for IGF1R in the absence of the latter. Conclusions These results define the molecular components that are responsible for a major burst of cardiomyocyte proliferation during heart development. These results may also be relevant to understanding the efficiency of regeneration of the mammalian heart after neonatal and adult injury. |
topic |
Heart development Epicardium IGF2 IGF1R Insulin receptor Cardiomyocyte proliferation |
url |
http://link.springer.com/article/10.1186/s12861-019-0186-8 |
work_keys_str_mv |
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