Interrenal Organogenesis in the Zebrafish Model

Abstract

In recent years, many genes that participate in the specification, differentiation and steroidogenesis of the interrenal organ, the teleostean homologue of the adrenal cortex, have been identified and characterized in zebrafish. In-depth studies of these genes have helped to delineate the morphogenetic steps of interrenal organ formation, as well as some of the molecular and cellular mechanisms that govern these processes. The codevelopment of interrenal tissue with the embryonic kidney (pronephros), surrounding endothelium and invading chromaffin cells has been analyzed, by virtue of the amenability of zebrafish embryos to a variety of genetic, developmental and histological approaches. Moreover, zebrafish embryos can be subject to molecular as well as biochemical assays for the unraveling of the transcriptional regulation program underlying interrenal development. To this end, the key mechanisms that control organogenesis and steroidogenesis of the zebrafish interrenal gland have been shown to resemble those in mammals, justifying the future utilization of zebrafish model for discovering novel genes associated with adrenal development and disease.

Wt1a, Foxc1a, and the Notch mediator Rbpj physically interact and regulate the formation of podocytes in zebrafish

“…Arising in close proximity to podocytes are interrenal gland cells, the teleost equivalent of the adrenal gland in mammals (Liu, 2007). The earliest marker of these cells is nr5a1a (also known as ff1b ), a member of the Ftz-F1 nuclear receptor family, which initiates at the 22-somite stage (20 hpf) and is critical for interrenal gland specification (Hsu et al, 2003).…”

Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish

“…ACTH is produced by posttranslational modification of protein encoded by the gene proopiomelanocortin ( pomc ) 1 3 ACTH binds to the melanocortin 2 receptor (MC2R) on the steroidogenic cells of the interrenal tissue and activates cortisol biosynthesis and secretion 3 4 . The interrenal tissue is analogous to the adrenal gland in higher vertebrates 5 and cortisol is the primary circulating glucocorticoid in fish. Cortisol has a variety of effects in teleosts, but its most well-studied function in response to stress is to enhance metabolic capacity and mobilize energy stores to restore homeostasis 3 .…”

Scaling up to study brca2: the zeppelin zebrafish mutant reveals a role for brca2 in embryonic development of kidney mesoderm

“…In exploring related tissue types, we noticed a significant increase in area and volume of the interrenal gland (IR) in zep mutants, the teleost equivalent of the adrenal cortex, which is marked by the transcripts of nuclear receptor subfamily 5, group A, member 1a ( nr5a1a) at 36 hpf (Figure 1D). This expansion was verified by 3β-hydroxysteroid dehydrogenase (3β-HSD) chromogenic staining, which indicates an enzymatic property of differentiated IR cells [67] . In previous studies, it has been shown that podocytes and IR cells arise from the wt1a progenitor field, and that knockdown of wt1a leads to a decrease in IR size [67, 68] .…”

“…This expansion was verified by 3β-hydroxysteroid dehydrogenase (3β-HSD) chromogenic staining, which indicates an enzymatic property of differentiated IR cells [67] . In previous studies, it has been shown that podocytes and IR cells arise from the wt1a progenitor field, and that knockdown of wt1a leads to a decrease in IR size [67, 68] . Because there was no distinguishable difference in proliferation and cell death, we hypothesized that the cells that would normally be predestined for the podocyte lineage in the wt1a -expressing renal progenitor field undergo a fate change to the IR lineage in the zep mutants.…”