Abstract 17120: Mir-130a Modulates Vascular Patterning During Embryogenesis
Remodeling of the pre-existing primitive vasculature is necessary for the formation of a complex branched vascular architecture; however the factors that modulate these processes are incompletely defined. Etv2 (Ets-family transcription factor) marks the earliest endothelial progenitors during development. Utilizing Etv2-Cre, we conditionally deleted Dicer allele to define the role of Dicer and microRNAs in vascular development and patterning. Etv2-Cre mediated ablation of Dicer resulted in embryonic lethality with defective vascular plexuses and impaired vascular patterning in the embryo proper and yolk-sac. We previously reported Etv2-miR-130a cascade in the regulation of mesodermal specification. Herein, we showed involvement of endothelial-enriched microRNA, miR-130a, in mediating vascular patterning and angiogenesis in vitro and in vivo. Doxycline-mediated forced overexpression of miR-130a resulted in robust induction of vascular sprouts and angiogenesis with increased uptake of acetylated-LDL. In contrast, targeted deletion of miR-130a (miR-130a-/-) using CRISPR/Cas9 technology showed significantly reduced endothelial transcripts during ES/EB differentiation. Further injection miR-130a specific morpholinos in zebrafish embryos resulted in defective vasculature, reduced inter-somitic vessel and perturbed vascular patterning. Consistent with these results, qPCR and in situ hybridization experiments showed reduced levels of endothelial transcripts in the miR-130a morphants. These findings demonstrate a critical role for Dicer and miR-130a in endothelial development and patterning.
Author Disclosures: B.N. Singh: None. N. Tahara: None. S. Das: None. M. Garry: None. W. Gong: None. Y. Kawakami: None. N. Koyano-Nakagawa: None. D. Garry: None.
- © 2016 by American Heart Association, Inc.