Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

MicroRNAs are a well-studied class of non-coding RNA and are known to regulate developmental processes in eukaryotes. Their role in key biological processes such as vasculature development has attracted interest. However, a comprehensive understanding of molecular regulation of angiogenesis and vascular integrity during development remains less explored. Here we identified miRNAs involved in the development and maintenance of vasculature in zebrafish embryos using a reverse genetics approach. Using a combination of bioinformatics predictions and literature based evidences we mined over 701 Human and 329 Zebrafish miRNAs to derive a list of 29 miRNAs targeting vascular specific genes in zebrafish. We shortlisted eight miRNAs and investigated their potential role in regulating vascular development in zebrafish transgenic model. In this screen we identified three miRNAs, namely miR-1, miR-144 and miR-142a-3p that have the potential to influence vascular development in zebrafish. We show that miR-142a-3p mediates vascular integrity and developmental angiogenesis in vivo. Overexpression of miR-142a-3p results in loss of vascular integrity, hemorrhage and vascular remodeling during zebrafish embryonic development, while loss of function of miR-142a-3p causes abnormal vascular remodeling. MiR-142a-3p functions in part by directly repressing cdh5 (VE-cadherin). The vascular abnormalities that results from modulation of miR-142a-3p are reminiscent of cdh5 perturbation in zebrafish embryos. We also demonstrate that the action of miR-142a on cdh5 is potentially regulated by Lmo2, an important transcription factor, known for its role in vasculature development. The miR142a-3p mediated control of cdh5 constitutes an additional layer of regulation for maintaining vascular integrity and developmental angiogenesis. These findings have implications in development, wound repair and tumor growth.

Original publication

DOI

10.1371/journal.pone.0052588

Type

Journal article

Journal

PLoS One

Publication Date

2012

Volume

7

Keywords

Animals, Antigens, CD, Base Sequence, Binding Sites, Blood Vessels, Cadherins, Computational Biology, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Genetic Testing, Hemorrhage, Humans, LIM Domain Proteins, MicroRNAs, Molecular Sequence Data, Neovascularization, Physiologic, Phenotype, Protein Binding, Reverse Genetics, Transcription Factors, Zebrafish, Zebrafish Proteins