| IGF signaling directs ventricular cardiomyocyte proliferation during embryonic heart development. | |
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MedLine Citation:
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PMID: 21429986 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Secreted factors from the epicardium are believed to be important in directing heart ventricular cardiomyocyte proliferation and morphogenesis, although the specific factors involved have not been identified or characterized adequately. We found that IGF2 is the most prominent mitogen made by primary mouse embryonic epicardial cells and by a newly derived immortalized mouse embryonic epicardial cell line called MEC1. In vivo, Igf2 is expressed in the embryonic mouse epicardium during midgestation heart development. Using a whole embryo culture assay in the presence of inhibitors, we confirmed that IGF signaling is required to activate the ERK proliferation pathway in the developing heart, and that the epicardium is required for this response. Global disruption of the Igf2 gene, or conditional disruption of the two IGF receptor genes Igf1r and Insr together in the myocardium, each resulted in a significant decrease in ventricular wall proliferation and in ventricular wall hypoplasia. Ventricular cardiomyocyte proliferation in mutant embryos was restored to normal at E14.5, concurrent with the establishment of coronary circulation. Our results define IGF2 as a previously unexplored epicardial mitogen that is required for normal ventricular chamber development. |
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Authors:
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Peng Li; Susana Cavallero; Ying Gu; Tim H P Chen; Jennifer Hughes; A Bassim Hassan; Jens C Brüning; Mohammad Pashmforoush; Henry M Sucov |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-03-23 |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 138 ISSN: 1477-9129 ISO Abbreviation: Development Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-13 Completed Date: 2011-07-01 Revised Date: 2012-09-24 |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 1795-805 Citation Subset: IM |
Affiliation:
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Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation* / drug effects Cells, Cultured Embryo, Mammalian Gene Expression Regulation, Developmental / drug effects Heart / drug effects, embryology* Heart Ventricles / cytology, metabolism Insulin-Like Growth Factor II / genetics, metabolism, pharmacology, physiology* Mice Mice, Inbred ICR Mice, Transgenic Myocardium / metabolism Myocytes, Cardiac / drug effects, metabolism, physiology* RNA, Small Interfering / pharmacology Receptor, IGF Type 2 / genetics, metabolism, physiology Signal Transduction / drug effects, genetics, physiology |
| Grant Support | |
ID/Acronym/Agency:
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HL070123/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Small Interfering; 0/Receptor, IGF Type 2; 67763-97-7/Insulin-Like Growth Factor II |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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