Reverse genetics screen in zebrafish identifies a role of miR-142a-3p in vascular development and integrity

Autor: Vinod Scaria, Ashok Patowary, Rajendra K. Chauhan, Sridhar Sivasubbu, Meenakshi Sharma, Mukesh Kumar Lalwani, Naresh Singh, Angom Ramcharan Singh
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Genetic Screens
Anatomy and Physiology
Embryo
Nonmammalian
Morpholino
Angiogenesis
lcsh:Medicine
Bioinformatics
Cardiovascular System
Nucleic Acids
Molecular Cell Biology
lcsh:Science
Zebrafish
Regulation of gene expression
Multidisciplinary
biology
Gene Expression Regulation
Developmental
Genomics
Animal Models
LIM Domain Proteins
Cadherins
Phenotype
Cell biology
Research Article
Protein Binding
Molecular Sequence Data
Neovascularization
Physiologic
Hemorrhage
Model Organisms
Genome Analysis Tools
Antigens
CD
microRNA
Genetics
Animals
Humans
Genetic Testing
Transcription factor
Biology
Loss function
Binding Sites
Base Sequence
lcsh:R
Computational Biology
Zebrafish Proteins
biology.organism_classification
Reverse Genetics
MicroRNAs
Cardiovascular Anatomy
RNA
Blood Vessels
lcsh:Q
Organism Development
Developmental Biology
Transcription Factors
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 12, p e52588 (2012)
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: