PUBLICATION

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
Abstract

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.

Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes