PUBLICATION

Slc39a5-mediated zinc homeostasis plays an essential role in venous angiogenesis in zebrafish

Authors
Xia, Z., Bi, X., Lian, J., Dai, W., He, X., Zhao, L., Min, J., Wang, F.
ID
ZDB-PUB-201022-4
Date
2020
Source
Open Biology   10: 200281 (Journal)
Registered Authors
Keywords
Slc39a5, angiogenesis, zebrafish, zinc homeostasis
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Cation Transport Proteins/chemistry
  • Cation Transport Proteins/genetics
  • Cation Transport Proteins/metabolism*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Homeostasis*
  • Mice, Transgenic
  • Neovascularization, Physiologic*/genetics
  • Phenotype
  • Zebrafish/physiology*
  • Zinc/metabolism*
PubMed
33081634 Full text @ Open Biol.
Abstract
Angiogenesis is a precise process mediated by a variety of signals and the environmental niche. Although the essential trace element zinc and its homeostasis are essential for maintaining proper cellular functions, whether zinc plays a role in angiogenesis is currently unknown. Using zebrafish embryos as a model system, we found that zinc treatment significantly increased the expression of the slc39a5 gene, which encodes the zinc transporter Slc39a5. Moreover, knocking down slc39a5 expression using either a morpholino or CRISPR/Cas9-mediated gene editing led to cardiac ischaemia and an accumulation of red blood cells in the caudal vein plexus (CVP), as well as delayed venous sprouting and fewer vascular loops in the CVP region during early development. Further analysis revealed significantly reduced proliferation and delayed cell migration in the caudal vein of slc39a5 morphants. At the mechanistic level, we found increased levels of systemic zinc in slc39a5-deficient embryos, and chelating zinc restored CVP development. In addition, we found that zinc overload in wild-type embryos leads to impaired CVP formation. Taken together, these results indicate that Slc39a5 plays a critical role in endothelial sprouting and migration in venous angiogenesis by regulating zinc homeostasis.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping