Document Detail

miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation.
MedLine Citation:
PMID:  20018673     Owner:  NLM     Status:  MEDLINE    
MicroRNAs (miRNAs) have previously been implicated in a number of developmental processes, including development of the ventricular myocardium of the heart. To determine what, if any, additional roles miRNAs play in cardiogenesis, we deleted the miRNA-processing enzyme Dicer specifically in the developing murine heart. Embryos lacking cardiac Dicer lived longer than reported in previous studies using different alleles to remove cardiac Dicer activity and displayed a highly penetrant phenotype of double outlet right ventricle with a concurrent ventricular septal defect. Before the defect's onset, Pitx2c and Sema3c, both required for outflow tract morphogenesis, were up-regulated in Dicer-deficient hearts. Interestingly, mesenchymal apoptosis in the outflow tract normally required for outflow tract alignment was greatly decreased in the mutants, likely contributing directly to the observed phenotype. In sum, we demonstrate here a specific developmental process, that of outflow tract morphogenesis, being hindered by the deletion of miRNAs during cardiogenesis.
Ankur Saxena; Clifford J Tabin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-12-14
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-18     Completed Date:  2010-03-09     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  87-91     Citation Subset:  IM    
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MeSH Terms
Aorta / anatomy & histology,  embryology
Cell Death / physiology
Embryo, Mammalian / anatomy & histology,  physiology
Gene Deletion
Heart* / anatomy & histology,  embryology
Homeodomain Proteins / genetics,  metabolism
MicroRNAs / genetics,  metabolism*
Morphogenesis / physiology*
Myocardium / enzymology*
Ribonuclease III / genetics,  metabolism*
Semaphorins / genetics,  metabolism
Transcription Factors / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Homeodomain Proteins; 0/MicroRNAs; 0/Nkx2-5 protein, mouse; 0/Semaphorins; 0/Transcription Factors; 0/semaphorin 3C protein, mouse; 184787-43-7/homeobox protein PITX2; EC III

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