Title

miR-221 is required for endothelial tip cell behaviors during vascular development

UMMS Affiliation

Program in Gene Function and Expression; Program in Bioinformatics and Integrative Biology

Date

2-14-2012

Document Type

Article

Medical Subject Headings

MicroRNAs; Neovascularization, Physiologic

Disciplines

Genetics and Genomics

Abstract

Angiogenesis requires coordination of distinct cell behaviors between tip and stalk cells. Although this process is governed by regulatory interactions between the vascular endothelial growth factor (Vegf) and Notch signaling pathways, little is known about the potential role of microRNAs. Through deep sequencing and functional screening in zebrafish, we find that miR-221 is essential for angiogenesis. miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 receptor. Furthermore, miR-221 was required for tip cell proliferation and migration, as well as tip cell potential in mosaic blood vessels. miR-221 knockdown also prevented "hyper-angiogenesis" defects associated with Notch deficiency and miR-221 expression was inhibited by Notch signaling. Finally, miR-221 promoted tip cell behavior through repression of two targets: cyclin dependent kinase inhibitor 1b (cdkn1b) and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1). These results identify miR-221 as an important regulatory node through which tip cell migration and proliferation are controlled during angiogenesis.

Rights and Permissions

Citation: Dev Cell. 2012 Feb 14;22(2):418-29. Link to article on publisher's site

Related Resources

Link to Article in PubMed