Document Detail


MicroRNA-processing enzyme Dicer is required in epicardium for coronary vasculature development.
MedLine Citation:
PMID:  21969379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The epicardium is a sheet of epithelial cells covering the heart during early cardiac development. In recent years, the epicardium has been identified as an important contributor to cardiovascular development, and epicardium-derived cells have the potential to differentiate into multiple cardiac cell lineages. Some epicardium-derived cells that undergo epithelial-to-mesenchymal transition and delaminate from the surface of the developing heart subsequently invade the myocardium and differentiate into vascular smooth muscle of the developing coronary vasculature. MicroRNAs (miRNAs) have been implicated broadly in tissue patterning and development, including in the heart, but a role in epicardium is unknown. To examine the role of miRNAs during epicardial development, we conditionally deleted the miRNA-processing enzyme Dicer in the proepicardium using Gata5-Cre mice. Epicardial Dicer mutant mice are born in expected Mendelian ratios but die immediately after birth with profound cardiac defects, including impaired coronary vessel development. We found that loss of Dicer leads to impaired epicardial epithelial-to-mesenchymal transition and a reduction in epicardial cell proliferation and differentiation into coronary smooth muscle cells. These results demonstrate a critical role for Dicer, and by implication miRNAs, in murine epicardial development.
Authors:
Manvendra K Singh; Min Min Lu; Daniele Massera; Jonathan A Epstein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-21     Completed Date:  2012-01-16     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  41036-45     Citation Subset:  IM    
Affiliation:
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. masingh@mail.med.upenn.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / genetics
Coronary Vessels / cytology,  enzymology,  metabolism,  physiology*
Cytoskeleton / metabolism
Epithelial-Mesenchymal Transition / genetics
Female
GATA5 Transcription Factor / genetics
Gene Deletion
Integrases / metabolism
Male
Mice
Mice, Transgenic
MicroRNAs / metabolism*
Muscle, Smooth, Vascular / cytology,  metabolism
Neovascularization, Physiologic* / genetics
Pericardium / cytology,  enzymology*,  metabolism,  physiology
RNA Processing, Post-Transcriptional* / genetics
Ribonuclease III / deficiency,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
U01 HL100405/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/GATA5 Transcription Factor; 0/MicroRNAs; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases; EC 3.1.26.3/Ribonuclease III
Comments/Corrections

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