Unraveling the glucocorticoid receptor pathway in zebrafish

Abstract

Glucocorticoid receptor (GR) signaling is versatile and plays an essential role in the survival and well-being of organisms. Glucocorticoids are also widely used clinically in order to combat inflammatory medical conditions. In the present thesis we aimed at studying the GR pathway by means of stimulation with synthetic GCs and genetic manipulation. Since the GR is a transcription factor, our main readout for GR function in most of our experimental settings was transcriptome analysis. By gathering whole transcriptome information, we aimed at unraveling the molecular pathways affected by GR signaling in different physiological conditions, thus exploring its functional role. As a model organism we employed the zebrafish, since it allows fine genetic, molecular and cellular experimental approaches and its GR pathway closely resembles that of humans. Our aim was also to further characterize the function of this versatile signaling cascade in zebrafish, in order to establish this animal model as a valid system for detailed as well as high throughput research on GR, enabling us to test hypotheses and complement results obtained from other well-established experimental animal models such as rodents.