PUBLICATION

Metallothionein 2 regulates endothelial cell migration through transcriptional regulation of vegfc expression

Authors
Schuermann, A., Helker, C.S., Herzog, W.
ID
ZDB-PUB-150723-4
Date
2015
Source
Angiogenesis   18(4): 463-75 (Journal)
Registered Authors
Helker, Christian, Herzog, Wiebke
Keywords
Vegfc, Angiogenesis, Endothelial cell migration, TALEN, Nonsense-mediated decay, Phenotype variability, Zebrafish
MeSH Terms
  • Animals
  • Cell Movement/physiology*
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism*
  • Gene Expression Regulation, Developmental/physiology*
  • Metallothionein/genetics
  • Metallothionein/metabolism*
  • Neovascularization, Physiologic/physiology*
  • Transcription, Genetic/physiology*
  • Vascular Endothelial Growth Factor C/biosynthesis*
  • Vascular Endothelial Growth Factor C/genetics
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
PubMed
26198291 Full text @ Angiogenesis
Abstract
Analysis of developmental angiogenesis can help to identify regulatory networks, which also contribute to disease-related vascular growth. Vascular endothelial growth factors (Vegf) drive angiogenic processes such as sprouting, endothelial cell (EC) migration and proliferation. However, how Vegf expression is regulated during development is not well understood. By analyzing developmental zebrafish angiogenesis, we have identified Metallothionein 2 (Mt2) as a novel regulator of vegfc expression. While Metallothioneins (Mts) have been extensively analyzed for their capability of regulating homeostasis and metal detoxification, we demonstrate that Mt2 is required for EC migration, proliferation and angiogenic sprouting upstream of vegfc expression. We further demonstrate that another Mt family member cannot compensate Mt2 deficiency and therefore postulate that Mt2 regulates angiogenesis independent of its canonical Mt function. Our data not only reveal a non-canonical function of Mt2 in angiogenesis, but also propose Mt2 as a novel regulator of vegfc expression.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping