ZFIN ID: ZDB-PUB-130422-1
miR-21 represses Pdcd4 during cardiac valvulogenesis
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.
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.