Abstract 19652: Etv2/mir-130a/pdgfra Pathway Regulates Endothelial Lineage Specification
MicroRNAs (small non-coding RNAs) are known to regulate critical developmental stages during embryogenesis. In the present studies, we examined the role of the Etv2-miR-130a regulatory cascade and mesodermal specification. Conditional ablation of Dicer in the mesodermal derivatives including Mesp1-, Flk1- or Etv2-expressing precursors resulted in embryonic lethality. Deletion of Dicer in the endothelial progenitors resulted in embryos with impaired vascular plexuses, hemorrhage, and edema. We identified miR-130a as a direct target of Etv2 and demonstrated that it mediates endothelial lineage commitment. Forced overexpression of miR-130a promoted the endothelial program, whereas knockdown of miR-130a resulted in perturbed vascular branching and patterning and had no effect on the hematopoietic lineages. Furthermore, we demonstrated that miR-130a directly targets Pdgfra and promotes the endothelial program. This is the first report of a miRNA, which specifically promotes the divergence of a common progenitor to the endothelial lineage. Moreover, these studies enhance our understanding of the regulatory cascades that govern embryogenesis.
Key words: Lineage specification, vascular development, Etv2, miR-130a, Dicer
Author Disclosures: B.N. Singh: None. X. Shi: None. R. Akiyama: None. T. Rasmussen: None. Y. kawakami: None. N. Koyano-Nakagawa: None. D. Garry: None.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.