Discovery of a Functional Glucocorticoid Receptor β-Isoform in Zebrafish

Schaaf, Marcel J. M.; Champagne, Danielle L.; Laanen, Ivo H. C. van; Wijk, Diane C.W.A. van; Meijer, Annemarie H.; Meijer, Onno C.; Spaink, Herman P.; Richardson, Michael K.

doi:10.1210/en.2007-1364

Cited by 152 publications

(133 citation statements)

References 41 publications

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“…An advantage of the zebrafish as a model system for the screening of glucocorticoid drugs is the relatively high level of similarity between the human and zebrafish glucocorticoid system, as we have recently shown (Schaaf et al, 2008). First, the main endogenous glucocorticoid hormone in zebrafish is cortisol, as it is in humans.…”

Section: Glucocorticoid Drug Screensmentioning

confidence: 99%

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Zebrafish development and regeneration: new tools for biomedical research

Brittijn

Duivesteijn²,

Belmamoune³

et al. 2009

Int. J. Dev. Biol.

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145

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Basic research in pattern formation is concerned with the generation of phenotypes and tissues. It can therefore lead to new tools for medical research. These include phenotypic screening assays, applications in tissue engineering, as well as general advances in biomedical knowledge. Our aim here is to discuss this emerging field with special reference to tools based on zebrafish developmental biology. We describe phenotypic screening assays being developed in our own and other labs. Our assays involve: (i) systemic or local administration of a test compound or drug to zebrafish in vivo; (ii) the subsequent detection or "readout" of a defined phenotypic change. A positive readout may result from binding of the test compound to a molecular target involved in a developmental pathway. We present preliminary data on assays for compounds that modulate skeletal patterning, bone turnover, immune responses, inflammation and early-life stress. The assays use live zebrafish embryos and larvae as well as adult fish undergoing caudal fin regeneration. We describe proof-of-concept studies on the localised targeting of compounds into regeneration blastemas using microcarriers. Zebrafish are cheaper to maintain than rodents, produce large numbers of transparent eggs, and some zebrafish assays could be scaled-up into medium and high throughput screens. However, advances in automation and imaging are required. Zebrafish cannot replace mammalian models in the drug development pipeline. Nevertheless, they can provide a cost-effective bridge between cell-based assays and mammalian whole-organism models. KEY WORDS: Danio rerio, zebrafish, high-throughput screening, high-content screeningThis article is part of a special journal issue on "Pattern Formation". In this context, it seems appropriate to ask: 'what benefits to society can come from research into pattern formation?' The answer depends on how "pattern formation" is defined. For our purposes, it includes developmental mechanisms that generate Int. J. Dev. Biol. 53: 835-850 (2009) doi: 10.1387/ijdb.082615sb One is the field of human congenital malformations (the pres-836 S. A. Brittijn et al. ence at birth of anatomical abnormalities). Good examples are human malformations of fingers and toes, some cases of which are linked to mutations in the Hox family of developmental patterning genes (Akarsu et al., 1996;Goodman et al., 1997;Goodman, 2002). Teratology -the study of agents that cause congenital malformations -can be seen as applied pattern formation research. Tissue engineering, a medical research discipline that aims to create replacement tissues for patients who have suffered injury or surgical removal of tissues, is another area where knowledge of pattern formation can be applied. To date, the commonest approach to tissue engineering is to culture autologous cells on a synthetic template (Silva and Mooney, 2004). In the future, however, it may be possible to promote pattern formation by these cells so that they generate selforganised tissues or structures ...

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Section: Glucocorticoid Drug Screensmentioning

confidence: 99%

“…It appears that the zebrafish contains only the gene encoding GR2, making it unique among well-studied fish species (Schaaf et al, 2008). The receptor that is encoded by this zebrafish GR gene shows a high level of similarity with the human GR (Fig.…”

Section: Glucocorticoid Drug Screensmentioning

confidence: 99%

Zebrafish development and regeneration: new tools for biomedical research

Brittijn

Duivesteijn²,

Belmamoune³

et al. 2009

Int. J. Dev. Biol.

Self Cite

145

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“…Zebrafish is peculiar, because it is the only fish known to have a single functional gr gene, while generally teleosts possess two grs, due to a genome duplication event that occurred in the taxon 350 million years ago. Apparently, the paralog gene was lost, but zebrafish expresses a splice variant of Gr, named Grb, acting as a dominant-negative inhibitor of the corticoid-activated Gr, as found only in humans (Schaaf et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The knockdown of maternal glucocorticoid receptor mRNA alters embryo development in zebrafish

et al. 2011

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In zebrafish, ovulated oocytes contain both maternal cortisol and the mRNA for the glucocorticoid receptor (gr), which is spread as granular structures throughout the ooplasm. At 0.2 hpf, this transcript is relocated in the blastodisc area and partitioned among blastomeres. At 6-8 hpf, it is replaced by zygotic transcript. We used morpholinos to block translation of both maternal and zygotic gr transcripts, and a missplicing morpholino to block post-transcriptionally the zygotic transcript alone. Only knockdown of translation produced an increase of apoptosis and subsequent craniofacial and caudal deformities with severe malformations of neural, vascular, and visceral organs in embryos and 5-dpf larvae. Such defects were rescued with trout gr2 mRNA. Microarray analysis revealed that 114 and 37 highly expressed transcripts were up-and down-regulated, respectively, by maternal Gr protein deficiency in 5-hpf embryos. These results indicate that the maternal gr transcript and protein participate in the maternal programming of zebrafish development. Developmental Dynamics 240:874-889,

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“…Two isoforms of the glucocorticoid receptors (alpha and beta) were identified in zebrafish. GRa is the main receptor binding dexamethasone and Cort, while GRb is a splice variant that inhibits GRa (Schaaf et al 2008). The available data about the presence and functionality of the receptors provide first indications that stress hormones might have a particular role during oogenesis in teleost fish.…”

Section: Introductionmentioning

confidence: 99%

Morphological and molecular effects of cortisol and ACTH on zebrafish stage I and II follicles

et al. 2015

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Oogenesis in zebrafish (Danio rerio) is controlled by the hypothalamus-pituitary-gonadal axis and reproductive hormones. In addition, an interference of stress hormones is known with reproductive biology. In the presented work, we aimed to explore the hypothesis that cortisol (Cort) and ACTH may affect early oogenesis in zebrafish, given the presence of the specific receptors for glucocorticoids and ACTH in the zebrafish ovary. Follicles at stages I and II were exposed in vitro to 1 mM Cort and ACTH for 48 h, then ultrastructural and molecular effects were analyzed. The comet assay demonstrated increased tail moments for Cort and ACTH treatment indicative of DNA damage. The mRNA expression of apoptotic genes (bax, bcl-2) was not altered by both treatments, but Cort increased significantly the expression of the ACTH receptor (mc2r). Cort stimulated the presence of the endoplasmic reticulum, predominantly at stage II, while ACTH induced a strong vacuolization. Viability of oocytes was not affected by both treatments and fluorescent staining (monodansylcadaverine/acridine orange) indicated a reduced quantity of autophagosomes for ACTH, and lower presence of nucleic acids in ooplasm for Cort and ACTH. Concluding, different responses were observed for stress hormones on early stages of zebrafish oocytes, which suggest a role for both hormones in the stress-mediated adverse effects on female gametogenesis. Reproduction (2015) 150 429-436

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Discovery of a Functional Glucocorticoid Receptor β-Isoform in Zebrafish

Cited by 152 publications

References 41 publications

Zebrafish development and regeneration: new tools for biomedical research

Zebrafish development and regeneration: new tools for biomedical research

The knockdown of maternal glucocorticoid receptor mRNA alters embryo development in zebrafish

Morphological and molecular effects of cortisol and ACTH on zebrafish stage I and II follicles

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