Insights into kidney stem cell development and regeneration using zebrafish

Drummond, B. J.; Wingert, Rebecca A.

doi:10.4252/wjsc.v8.i2.22

Cited by 21 publications

(15 citation statements)

References 107 publications

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“…The zebrafish pronephros is an experimentally tractable system to interrogate the genetic factors that regulate nephrogenesis because of its simple, conserved tubule structure, with two proximal segments and two distal segments (Figure 1A) (Ebarasi et al, 2011; Drummond and Wingert, 2016). The nephrons share a blood filter comprised of podocyte cells (P), followed by a neck (N) segment that transports fluid into the tubule, and finally a pronephric duct (PD) that drains caudally at the cloaca (C), a common exit for the kidney and gut in the embryo (Figure 1A, middle panel).…”

Section: Resultsmentioning

confidence: 99%

Prostaglandin signaling regulates nephron segment patterning of renal progenitors during zebrafish kidney development

Poureetezadi

Cheng

Chambers

et al. 2016

eLife

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Kidney formation involves patterning events that induce renal progenitors to form nephrons with an intricate composition of multiple segments. Here, we performed a chemical genetic screen using zebrafish and discovered that prostaglandins, lipid mediators involved in many physiological functions, influenced pronephros segmentation. Modulating levels of prostaglandin E2 (PGE2) or PGB2 restricted distal segment formation and expanded a proximal segment lineage. Perturbation of prostaglandin synthesis by manipulating Cox1 or Cox2 activity altered distal segment formation and was rescued by exogenous PGE2. Disruption of the PGE2 receptors Ptger2a and Ptger4a similarly affected the distal segments. Further, changes in Cox activity or PGE2 levels affected expression of the transcription factors irx3b and sim1a that mitigate pronephros segment patterning. These findings show for the first time that PGE2 is a regulator of nephron formation in the zebrafish embryonic kidney, thus revealing that prostaglandin signaling may have implications for renal birth defects and other diseases.DOI: http://dx.doi.org/10.7554/eLife.17551.001

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Section: Resultsmentioning

confidence: 99%

Prostaglandin signaling regulates nephron segment patterning of renal progenitors during zebrafish kidney development

Poureetezadi

Cheng

Chambers

et al. 2016

eLife

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“…In lower vertebrates, renal regeneration and structural remodeling occurs in response to injury due to the presence of potent renal progenitors. Interestingly, the presence of these progenitors can result in the formation of new nephrons during adult growth as well as during regeneration, in a process termed neonephrogenesis[4]. In stark contrast, mammals cease the generation of new nephrons at birth or shortly after[9].…”

Section: Fish As a Model To Study Renal Progenitors And Regenerationmentioning

confidence: 99%

“…Each human kidney contains up to 2 million functional units called nephrons that are divided into distinct epithelial segments[3]. Nephrons are organized within an intricate tissue architecture, where they are joined to a centralized collecting duct (CD) network for waste excretion[4]. Due to the complexity of the kidney, the coordination of developmental events that create nephrons and their surrounding interstitial populations from embryonic progenitor cells remains a key question in the biomedical field.…”

Section: Introductionmentioning

confidence: 99%

Renal progenitors: Roles in kidney disease and regeneration

Chambers

Wingert

2016

WJSC

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Kidney disease is a devastating condition that affects millions of people worldwide, and its prevalence is predicted to significantly increase. The kidney is a complex organ encompassing many diverse cell types organized in a elaborate tissue architecture, making regeneration a challenging feat. In recent years, there has been a surge in the field of stem cell research to develop regenerative therapies for various organ systems. Here, we review some recent progressions in characterizing the role of renal progenitors in development, regeneration, and kidney disease in mammals. We also discuss how the zebrafish provides a unique experimental animal model that can provide a greater molecular and genetic understanding of renal progenitors, which may contribute to the development of potential regenerative therapies for human renal afflictions.

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“…The embryonic kidney is just one essential organ that can be visualized in the zebrafish embryo at 24 hours post fertilization (hpf), known at this stage as the pronephros [26] . The pronephros has a simple anatomy, with two nephron functional units that perform excretory tasks beginning by the 48 hpf stage [27] .…”

Section: Introductionmentioning

confidence: 99%

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

Drummond

Wingert

2018

Can Cell Microenviron

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Specialized renal epithelial cells known as podocytes are essential components of the filtering structures within the kidney that coordinate the process of removing waste from the bloodstream. Podocyte loss initiates many human kidney diseases as it triggers subsequent damage to the kidney, leading to progressive loss of function that culminates with end stage renal failure. Podocyte morphology, function and gene expression profiles are well conserved between zebrafish and humans, making the former a relevant model to study podocyte development and model kidney diseases. Recently, we reported that whole genome sequencing of the zeppelin (zep) zebrafish mutant, which exhibits podocyte abrogation, revealed that the causative lesion for this defect was a splicing mutation in the breast cancer 2, early onset (brca2) gene. This was a surprising and novel discovery, as previous research on brca2/BRCA2 in a number of vertebrate animal models had not implicated an explicit role for this gene in kidney mesoderm development. Interestingly, the abrogation of the podocyte lineage in zep mutants was also accompanied by the formation of a larger interrenal (IR) gland, which is analogous to the adrenal gland in mammals, and suggested a fate switch between the renal and inter renal mesodermal derivatives. Mirroring these findings, knockdown of brca2 also recapitulated the loss of podocytes and increased IR population. In addition, brca2 overexpression was sufficient to partially rescue podocytes in zep mutants, and induced ectopic podocyte formation in wild-type embryos. Interestingly, immunofluorescence studies indicated that zep mutants had elevated P-h2A.X levels, suggesting that DNA repair is dysfunctional in these animals and contributes to the zep phenotype. Moving forward, this unique zebrafish mutant provides a new model to further explore how brca2 contributes to the development of tissues including the kidney mesoderm—roles which may have implications for renal diseases as well.

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Insights into kidney stem cell development and regeneration using zebrafish

Cited by 21 publications

References 107 publications

Prostaglandin signaling regulates nephron segment patterning of renal progenitors during zebrafish kidney development

Prostaglandin signaling regulates nephron segment patterning of renal progenitors during zebrafish kidney development

Renal progenitors: Roles in kidney disease and regeneration

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

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