miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation
- Creators
- Saxena, Ankur
- Tabin, Clifford J.
Abstract
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.
Additional Information
© 2010 by the National Academy of Sciences. Contributed by Clifford J. Tabin, November 9, 2009 (sent for review October 4, 2009). Published online before print December 14, 2009. The authors thank Dane Loeliger for technical assistance, Dr. Richard Harvey for Nkx2.5-Cre mice, and Dr. Jonathan Epstein for plasmids. This work was supported by National Institutes of Health Grant HD047360. Author contributions: A.S. and C.J.T. designed research; A.S. performed research; A.S. and C.J.T. analyzed data; and A.S. and C.J.T. wrote the paper.Attached Files
Published - Saxena2010p6980P_Natl_Acad_Sci_Usa.pdf
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Additional details
- PMCID
- PMC2806718
- Eprint ID
- 17415
- Resolver ID
- CaltechAUTHORS:20100208-112244969
- HD047360
- NIH
- Created
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2010-02-11Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field