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Dev Biol
2008 Feb 15;3142:261-75. doi: 10.1016/j.ydbio.2007.11.025.
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Zebrafish mutations affecting cilia motility share similar cystic phenotypes and suggest a mechanism of cyst formation that differs from pkd2 morphants.
Sullivan-Brown J
,
Schottenfeld J
,
Okabe N
,
Hostetter CL
,
Serluca FC
,
Thiberge SY
,
Burdine RD
.
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Zebrafish are an attractive model for studying the earliest cellular defects occurring during renal cyst formation because its kidney (the pronephros) is simple and genes that cause cystic kidney diseases (CKD) in humans, cause pronephric dilations in zebrafish. By comparing phenotypes in three different mutants, locke, swt and kurly, we find that dilations occur prior to 48 hpf in the medial tubules, a location similar to where cysts form in some mammalian diseases. We demonstrate that the first observable phenotypes associated with dilation include cilia motility and luminal remodeling defects. Importantly, we show that some phenotypes common to human CKD, such as an increased number of cells, are secondary consequences of dilation. Despite having differences in cilia motility, locke, swt and kurly share similar cystic phenotypes, suggesting that they function in a common pathway. To begin to understand the molecular mechanisms involved in cyst formation, we have cloned the swt mutation and find that it encodes a novel leucine rich repeat containing protein (LRRC50), which is thought to function in correct dynein assembly in cilia. Finally, we show that knock-down of polycystic kidney disease 2 (pkd2) specifically causes glomerular cysts and does not affect cilia motility, suggesting multiple mechanisms exist for cyst formation.
Avner,
Abnormal sodium pump distribution during renal tubulogenesis in congenital murine polycystic kidney disease.
1992, Pubmed
Avner,
Abnormal sodium pump distribution during renal tubulogenesis in congenital murine polycystic kidney disease.
1992,
Pubmed
Badano,
The ciliopathies: an emerging class of human genetic disorders.
2006,
Pubmed
Baert,
Hereditary polycystic kidney disease (adult form): a microdissection study of two cases at an early stage of the disease.
1978,
Pubmed
Bernstein,
Glomerulocystic kidney disease--nosological considerations.
1993,
Pubmed
Bisgrove,
Polaris and Polycystin-2 in dorsal forerunner cells and Kupffer's vesicle are required for specification of the zebrafish left-right axis.
2005,
Pubmed
,
Xenbase
Bisgrove,
The roles of cilia in developmental disorders and disease.
2006,
Pubmed
Blacque,
Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport.
2006,
Pubmed
Brand,
Mutations affecting development of the midline and general body shape during zebrafish embryogenesis.
1996,
Pubmed
Brill,
Immunolocalization of ion transport proteins in human autosomal dominant polycystic kidney epithelial cells.
1996,
Pubmed
Burn,
Analysis of the genomic sequence for the autosomal dominant polycystic kidney disease (PKD1) gene predicts the presence of a leucine-rich repeat. The American PKD1 Consortium (APKD1 Consortium).
1995,
Pubmed
Drummond,
Making a zebrafish kidney: a tale of two tubes.
2003,
Pubmed
Drummond,
Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function.
1998,
Pubmed
Fischer,
Defective planar cell polarity in polycystic kidney disease.
2006,
Pubmed
Freshour,
Chlamydomonas flagellar outer row dynein assembly protein ODA7 interacts with both outer row and I1 inner row dyneins.
2007,
Pubmed
Gabow,
Autosomal dominant polycystic kidney disease.
1993,
Pubmed
Haffter,
The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio.
1996,
Pubmed
Hildebrandt,
Nephronophthisis-associated ciliopathies.
2007,
Pubmed
Ibraghimov-Beskrovnaya,
Targeting dysregulated cell cycle and apoptosis for polycystic kidney disease therapy.
2007,
Pubmed
Kamiya,
Mutations at twelve independent loci result in absence of outer dynein arms in Chylamydomonas reinhardtii.
1988,
Pubmed
Kramer-Zucker,
Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis.
2005,
Pubmed
Lacy,
Flagellar cells and ciliary cells in the renal tubule of elasmobranchs.
1989,
Pubmed
Liao,
Simple sequence-length polymorphism analysis.
1999,
Pubmed
Liu,
Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros.
2007,
Pubmed
Ma,
Jagged2a-notch signaling mediates cell fate choice in the zebrafish pronephric duct.
2007,
Pubmed
Menezes,
Molecular and cellular pathogenesis of autosomal recessive polycystic kidney disease.
2006,
Pubmed
Nadasdy,
Proliferative activity of cyst epithelium in human renal cystic diseases.
1995,
Pubmed
Nakanishi,
Proximal tubular cysts in fetal human autosomal recessive polycystic kidney disease.
2000,
Pubmed
NULL,
Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium.
1995,
Pubmed
NULL,
The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. The European Polycystic Kidney Disease Consortium.
1994,
Pubmed
Obara,
Polycystin-2 immunolocalization and function in zebrafish.
2006,
Pubmed
Omori,
oko meduzy and related crumbs genes are determinants of apical cell features in the vertebrate embryo.
2006,
Pubmed
Onuchic,
PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats.
2002,
Pubmed
Perrone,
Extrarenal manifestations of ADPKD.
1997,
Pubmed
Praetorius,
Bending the primary cilium opens Ca2+-sensitive intermediate-conductance K+ channels in MDCK cells.
2003,
Pubmed
Praetorius,
Bending the MDCK cell primary cilium increases intracellular calcium.
2001,
Pubmed
Ramasubbu,
Increased epithelial cell proliferation and abnormal extracellular matrix in rat polycystic kidney disease.
1998,
Pubmed
Schottenfeld,
Zebrafish curly up encodes a Pkd2 ortholog that restricts left-side-specific expression of southpaw.
2007,
Pubmed
Serluca,
Pre-pattern in the pronephric kidney field of zebrafish.
2001,
Pubmed
Shillingford,
The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease.
2006,
Pubmed
Simons,
Polycystic kidney disease: cell division without a c(l)ue?
2006,
Pubmed
Sun,
A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney.
2004,
Pubmed
,
Xenbase
Tanner,
Atubular glomeruli in a rat model of polycystic kidney disease.
2002,
Pubmed
Thomson,
Histopathological analysis of renal cystic epithelia in the Pkd2WS25/- mouse model of ADPKD.
2003,
Pubmed
Torres,
Mechanisms of Disease: autosomal dominant and recessive polycystic kidney diseases.
2006,
Pubmed
Torres,
Polycystic kidney disease: genes, proteins, animal models, disease mechanisms and therapeutic opportunities.
2007,
Pubmed
Verani,
Histogenesis of the renal cysts in adult (autosomal dominant) polycystic kidney disease: a histochemical study.
1988,
Pubmed
Vize,
Model systems for the study of kidney development: use of the pronephros in the analysis of organ induction and patterning.
1997,
Pubmed
,
Xenbase
Ward,
The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein.
2002,
Pubmed
Wilson,
Apical plasma membrane mispolarization of NaK-ATPase in polycystic kidney disease epithelia is associated with aberrant expression of the beta2 isoform.
2000,
Pubmed
Wilson,
Polycystic kidney disease.
2004,
Pubmed
Wingert,
The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros.
2007,
Pubmed
,
Xenbase
Wu,
Cardiac defects and renal failure in mice with targeted mutations in Pkd2.
2000,
Pubmed
Yamaguchi,
Cyclic AMP activates B-Raf and ERK in cyst epithelial cells from autosomal-dominant polycystic kidneys.
2003,
Pubmed
Zerres,
Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): molecular genetics, clinical experience, and fetal morphology.
1998,
Pubmed
Zhao,
Genetic defects of pronephric cilia in zebrafish.
2007,
Pubmed
