miR-21 represses Pdcd4 during cardiac valvulogenesis
- Authors
- Kolpa, H.J., Peal, D.S., Lynch, S.N., Giokas, A.C., Ghatak, S., Misra, S., Norris, R.A., MacRae, C.A., Markwald, R.R., Ellinor, P., Bischoff, J., and Milan, D.J.
- ID
- ZDB-PUB-130422-1
- Date
- 2013
- Source
- Development (Cambridge, England) 140(10): 2172-80 (Journal)
- Registered Authors
- Ellinor, Patrick, MacRae, Calum A., Milan, David J.
- Keywords
- none
- MeSH Terms
-
- Animals
- Apoptosis Regulatory Proteins/metabolism*
- Cell Movement
- Crosses, Genetic
- Endothelial Cells/cytology
- Gene Expression Regulation, Developmental*
- Heart Valves/embryology*
- Humans
- Mice
- MicroRNAs/metabolism*
- RNA-Binding Proteins/metabolism*
- Time Factors
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 23578931 Full text @ Development
The discovery of small non-coding microRNAs has revealed novel mechanisms of post-translational regulation of gene expression, the implications of which are still incompletely understood. We focused on microRNA 21 (miR-21), which is expressed in cardiac valve endothelium during development, in order to better understand its mechanistic role in cardiac valve development. Using a combination of in vivo gene knockdown in zebrafish and in vitro assays in human cells, we show that miR-21 is necessary for proper development of the atrioventricular valve (AV). We identify pdcd4b as a relevant in vivo target of miR-21 and show that protection of pdcd4b from miR-21 binding results in failure of AV development. In vitro experiments using human pulmonic valve endothelial cells demonstrate that miR-21 overexpression augments endothelial cell migration. PDCD4 knockdown alone was sufficient to enhance endothelial cell migration. These results demonstrate that miR-21 plays a necessary role in cardiac valvulogenesis, in large part due to an obligatory downregulation of PDCD4.