Document Detail

IGF signaling directs ventricular cardiomyocyte proliferation during embryonic heart development.
MedLine Citation:
PMID:  21429986     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-23
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  138     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-13     Completed Date:  2011-07-01     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  1795-805     Citation Subset:  IM    
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MeSH Terms
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, 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
9891//Cancer Research UK; HL070123/HL/NHLBI NIH HHS
Reg. No./Substance:
0/RNA, Small Interfering; 0/Receptor, IGF Type 2; 67763-97-7/Insulin-Like Growth Factor II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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