Open AccessBidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae
Author(s) -
Davide Marchi,
Kirankumar Santhakumar,
Eleanor Markham,
Nan Li,
KarlHeinz Storbeck,
Nils Krone,
Vincent T. Cunliffe,
Fredericus J.M. van Eeden
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1008757
Subject(s) - glucocorticoid receptor , glucocorticoid , biology , crosstalk , mineralocorticoid receptor , zebrafish , in vivo , microbiology and biotechnology , endogeny , receptor , hypoxia (environmental) , hypoxia inducible factors , signalling , hedgehog signaling pathway , signal transduction , endocrinology , genetics , gene , chemistry , physics , organic chemistry , oxygen , optics
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 .