Kidney Development and Disease in the Zebrafish

Drummond, Iain A.

doi:10.1681/asn.2004090754

Cited by 172 publications

(130 citation statements)

References 45 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…Nephrogenesis in the zebrafish has a remarkable degree of similarity of organ cell types compared with higher vertebrates and numerous gene mutants have a correlate in human renal disease. [32][33][34][35] We demonstrate that the mutations identified in RHD patients reduce or eliminate the function of Six2 and Bmp4 in a zebrafish overexpression assay. A similar approach has been used to confirm that human mutations in CFC1 and TDGF1 result in loss of protein function.…”

Section: Overexpression Assaymentioning

confidence: 75%

SIX2 and BMP4 Mutations Associate With Anomalous Kidney Development

Weber

Taylor

Winyard

et al. 2008

Journal of the American Society of Nephrology

180

138

View full text Add to dashboard Cite

Renal hypodysplasia (RHD) is characterized by reduced kidney size and/or maldevelopment of the renal tissue following abnormal organogenesis. Mutations in renal developmental genes have been identified in a subset of affected individuals. Here, we report the first mutations in BMP4 and SIX2 identified in patients with RHD. We detected 3 BMP4 mutations in 5 RHD patients, and 3 SIX2 mutations in 5 different RHD patients. Overexpression assays in zebrafish demonstrated that these mutations affect the function of Bmp4 and Six2 in vivo. Overexpression of zebrafish six2.1 and bmp4 resulted in dorsalization and ventralization, respectively, suggesting opposing roles in mesendoderm formation. When mutant constructs containing the identified human mutations were overexpressed instead, these effects were attenuated. Morpholino knockdown of bmp4 and six2.1 affected glomerulogenesis, suggesting specific roles for these genes in the formation of the pronephros. In summary, these studies implicate conserved roles for Six2 and Bmp4 in the development of the renal system. Defects in these proteins could affect kidney development at multiple stages, leading to the congenital anomalies observed in patients with RHD.

show abstract

Section: Overexpression Assaymentioning

confidence: 75%

SIX2 and BMP4 Mutations Associate With Anomalous Kidney Development

Weber

Taylor

Winyard

et al. 2008

Journal of the American Society of Nephrology

180

138

View full text Add to dashboard Cite

show abstract

“…In terms of investigating developmental toxins, embryos of various teleost fish have been specifically explored as potential models for vertebrate development (e.g. Berman et al, 2005;Drummond, 2005;Morris and Fadool, 2005;Puffett-Lugassay and Zon, 2005;Sherwood and Wu, 2005), and consequently for the investigation of toxins that disrupt the pathways and processes related to development. Of these, the embryo of the zebrafish (Danio rerio) is finding considerably utility owing to a number of practical advantages.…”

Section: Introductionmentioning

confidence: 99%

The zebrafish (Danio rerio) embryo as a model system for identification and characterization of developmental toxins from marine and freshwater microalgae

Berry

Gantar

Gibbs

et al. 2007

Comparative Biochemistry and Physiology Part C: Toxicology &

109

View full text Add to dashboard Cite

The zebrafish (Danio rerio) embryo has emerged as an important model of vertebrate development. As such, this model system is finding utility in the investigation of toxic agents that inhibit, or otherwise interfere with, developmental processes (i.e. developmental toxins), including compounds that have potential relevance to both human and environmental health, as well as biomedicine. Recently, this system has been applied increasingly to the study of microbial toxins, and more specifically, as an aquatic animal model, has been employed to investigate toxins from marine and freshwater microalgae, including those classified among the so-called "harmful algal blooms" (HABs). We have developed this system for identification and characterization of toxins from cyanobacteria (i.e. "blue-green algae") isolated from the Florida Everglades and other freshwater sources in South and Central Florida. Here we review the use of this system as it has been applied generally to the investigation of toxins from marine and freshwater microalgae, and illustrate this utility as we have applied it to the detection, bioassay-guided fractionation and subsequent characterization of developmental toxins from freshwater cyanobacteria.

show abstract

“…The zebrafish is developing as a valid model for investigating human cystic kidney diseases [4]. The zebrafish pronephros develops after 2 days post-fertilisation (dpf), and the presence of cysts is easily screened at 3 dpf.…”

Section: Introductionmentioning

confidence: 99%

Restoration of renal function in zebrafish models of ciliopathies

Tobin¹,

Beales²

2008

Pediatr Nephrol

View full text Add to dashboard Cite

The ciliopathies are a class of rare human genetic disease whose aetioligies lie in defective primary cilia. Typical ciliopathies include Bardet-Biedl syndrome (BBS), nephronophthisis (NPHP), Jeune, Joubert, oro-facial-digital (OFD1) and Meckel (MKS) syndromes. All ciliopathies have the common denominator of renal disease, often including tubular cysts. In this study, we have modelled a range of ciliopathies in zebrafish and shown in all cases that knocking down these genes causes cystic lesions in the kidney. We have identified two drugs, rapamycin and roscovitine, which ameliorate the renal phenotype, both morphologically and functionally. This is the first study in which zebrafish has been used to identify potential therapeutic modalities for ciliopathic renal disease, and the results pave the way for further investigations in mammalian models.

show abstract

Kidney Development and Disease in the Zebrafish

Cited by 172 publications

References 45 publications

SIX2 and BMP4 Mutations Associate With Anomalous Kidney Development

SIX2 and BMP4 Mutations Associate With Anomalous Kidney Development

The zebrafish (Danio rerio) embryo as a model system for identification and characterization of developmental toxins from marine and freshwater microalgae

Restoration of renal function in zebrafish models of ciliopathies

Contact Info

Product

Resources

About