Morpholinos for splice modificatio

Morpholinos for splice modification


miR-21 represses Pdcd4 during cardiac valvulogenesis
Heather J. Kolpa, David S. Peal, Stacey N. Lynch, Andrea C. Giokas, Shibnath Ghatak, Suniti Misra, Russell A. Norris, Calum A. MacRae, Roger R. Markwald, Patrick Ellinor, Joyce Bischoff, David J. Milan


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.

  • Accepted March 11, 2013.
View Full Text