Reverse Genetics Screen in Zebrafish Identifies a Role of miR-142a-3p in Vascular Development and Integrity
IR@IGIB: CSIR-Institute of Genomics & Integrative Biology, New Delhi
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| Title |
Reverse Genetics Screen in Zebrafish Identifies a Role of
miR-142a-3p in Vascular Development and Integrity
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| Creator |
Lalwani, Mukesh K.
Sharma, Meenakshi Singh, Angom Ramcharan Chauhan, Rajendra Kumar Patowary , Ashok Singh, Naresh Scaria, Vinod Sivasubbu , Sridhar |
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| Subject |
CH1 Chemical Biology
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| Description |
Abstract
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.
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| Type |
Article
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://openaccess.igib.res.in/150/1/journal.pone.0052588.pdf
Lalwani, Mukesh K. and Sharma, Meenakshi and Singh, Angom Ramcharan and Chauhan, Rajendra Kumar and Patowary , Ashok and Singh, Naresh and Scaria, Vinod and Sivasubbu , Sridhar Reverse Genetics Screen in Zebrafish Identifies a Role of miR-142a-3p in Vascular Development and Integrity. Reverse Genetics Screen in Zebrafish Identifies a Role of miR-142a-3p in Vascular Development and Integrity. |
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| Relation |
http://openaccess.igib.res.in/150/
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