ZFIN ID: ZDB-PUB-140620-7
Zebrafish heart development is regulated via glutaredoxin 2 dependent migration and survival of neural crest cells
Berndt, C., Poschmann, G., Stühler, K., Holmgren, A., Bräutigam, L.
Date: 2014
Source: Redox Biology   2: 673-8 (Journal)
Registered Authors:
Keywords: A, atrium, CCV, common cardinal vein, CNC, cardiac neural crest, Cardiac development, GSH, glutathione, Glutaredoxin, Grx, glutaredoxin, Migration, NC, neural crest, S-glutathionylation, V, ventricle, Zebrafish, zf, zebrafish
MeSH Terms:
  • Animals
  • Apoptosis
  • Cell Movement
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development
  • Glutaredoxins/antagonists & inhibitors
  • Glutaredoxins/genetics
  • Glutaredoxins/metabolism*
  • Heart/growth & development*
  • Myocardium/metabolism
  • Neural Crest/cytology*
  • Neural Crest/metabolism
  • RNA Interference
  • RNA, Small Interfering/metabolism
  • Zebrafish/growth & development*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 24944912 Full text @ Redox Biol.
Glutaredoxin 2 is a vertebrate specific oxidoreductase of the thioredoxin family of proteins modulating the intracellular thiol pool. Thereby, glutaredoxin 2 is important for specific redox signaling and regulates embryonic development of brain and vasculature via reversible oxidative posttranslational thiol modifications. Here, we describe that glutaredoxin 2 is also required for successful heart formation. Knock-down of glutaredoxin 2 in zebrafish embryos inhibits the invasion of cardiac neural crest cells into the primary heart field. This leads to impaired heart looping and subsequent obstructed blood flow. Glutaredoxin 2 specificity of the observed phenotype was confirmed by rescue experiments. Active site variants of glutaredoxin 2 revealed that the (de)-glutathionylation activity is required for proper heart formation. Our data suggest that actin might be one target during glutaredoxin 2 regulated cardiac neural crest cell migration and embryonic heart development. In summary, this work represents further evidence for the general importance of redox signaling in embryonic development and highlights additionally the importance of glutaredoxin 2 during embryogenesis.