ZFIN ID: ZDB-PUB-200508-9
Bidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae
Marchi, D., Santhakumar, K., Markham, E., Li, N., Storbeck, K.H., Krone, N., Cunliffe, V.T., van Eeden, F.J.M.
Date: 2020
Source: PLoS Genetics   16: e1008757 (Journal)
Registered Authors: Cunliffe, Vincent, Marchi, Davide, Markham, Elenor R., Santhakumar, Kiran, van Eeden, Freek
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Aryl Hydrocarbon Receptor Nuclear Translocator/genetics
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/genetics
  • Glucocorticoids/metabolism
  • Glucocorticoids/pharmacology*
  • Hypoxia-Inducible Factor 1/metabolism
  • Hypoxia-Inducible Factor 1/physiology*
  • Larva/genetics
  • Larva/metabolism
  • Receptor Cross-Talk/drug effects
  • Receptor Cross-Talk/physiology*
  • Receptors, Glucocorticoid/metabolism
  • Receptors, Glucocorticoid/physiology
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Tumor Suppressor Proteins/genetics
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/growth & development
  • Zebrafish*/metabolism
  • Zebrafish Proteins/genetics
PubMed: 32379754 Full text @ PLoS Genet.
In the last decades in vitro studies highlighted the potential for crosstalk between Hypoxia-Inducible Factor-(HIF) and glucocorticoid-(GC) signalling pathways. However, how this interplay precisely occurs in vivo is still debated. Here, we use zebrafish larvae (Danio rerio) to elucidate how and to what degree hypoxic signalling affects the endogenous glucocorticoid pathway and vice versa, in vivo. Firstly, our results demonstrate that in the presence of upregulated HIF signalling, both glucocorticoid receptor (Gr) responsiveness and endogenous cortisol levels are repressed in 5 days post fertilisation larvae. In addition, despite HIF activity being low at normoxia, our data show that it already impedes both glucocorticoid activity and levels. Secondly, we further analysed the in vivo contribution of glucocorticoids to HIF activity. Interestingly, our results show that both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play a key role in enhancing it. Finally, we found indications that glucocorticoids promote HIF signalling via multiple routes. Cumulatively, our findings allowed us to suggest a model for how this crosstalk occurs in vivo.