PUBLICATION

miR-221 Is Required for Endothelial Tip Cell Behaviors during Vascular Development

Authors
Nicoli, S., Knyphausen, C.P., Zhu, L.J., Lakshmanan, A., and Lawson, N.D.
ID
ZDB-PUB-120223-3
Date
2012
Source
Developmental Cell   22(2): 418-429 (Journal)
Registered Authors
Lakshmanan, Abirami, Lawson, Nathan, Nicoli, Stefania
Keywords
none
Datasets
GEO:GSE35078
MeSH Terms
  • Animals
  • Biomarkers/metabolism
  • Blotting, Northern
  • Blotting, Western
  • Cell Movement*
  • Cell Proliferation
  • Cells, Cultured
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Endothelium, Vascular/cytology
  • Endothelium, Vascular/metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • MicroRNAs/physiology*
  • Neovascularization, Physiologic/physiology*
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylinositol 3-Kinases/metabolism
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism*
  • Signal Transduction
  • Vascular Endothelial Growth Factor C/metabolism
  • Vascular Endothelial Growth Factor Receptor-3/metabolism
  • Zebrafish/embryology
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism
(all 25)
PubMed
22340502 Full text @ Dev. Cell
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.

Genes / Markers
Figures
Figure Gallery (14 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
is19TgTransgenic Insertion
    la116TgTransgenic Insertion
      s916TgTransgenic Insertion
        sd2TgTransgenic Insertion
          um19
            Small Deletion
            um28TgTransgenic Insertion
              um63TgTransgenic Insertion
                y1TgTransgenic Insertion
                  y7TgTransgenic Insertion
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Fish
                    Antibodies
                    Orthology
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    DsRedEFGDsRed
                    EGFPEFGEGFP
                    GFPEFGGFP
                    mCherryEFGmCherry
                    TagRFPEFGTagRFP
                    1 - 5 of 5
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                    Mapping