spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
Development ePress online publication date 21 Jul 2004
doi: 10.1242/dev.01240

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.01240v1
131/16/4085    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sun, Z.
Right arrow Articles by Hopkins, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, Z.
Right arrow Articles by Hopkins, N.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research article: Development and disease

A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney


Zhaoxia Sun, Adam Amsterdam, Gregory J. Pazour, Douglas G. Cole, Mark S. Miller, and Nancy Hopkins*
* Author for correspondence (e-mail: nhopkins{at}mit.edu)

Polycystic kidney disease (PKD) is a common human genetic illness. It is characterized by the formation of multiple kidney cysts that are thought to result from over-proliferation of epithelial cells. Zebrafish larvae can also develop kidney cysts. In an insertional mutagenesis screen in zebrafish, we identified 12 genes that can cause cysts in the glomerular-tubular region when mutated and we cloned 10 of these genes. Two of these genes, vhnf1 (tcf2) and pkd2, are already associated with human cystic kidney diseases. Recently, defects in primary cilia have been linked to PKD. Strikingly, three out of the 10 genes cloned in this screen are homologues of Chlamydomonas genes that encode components of intraflagellar transport (IFT) particles involved in cilia formation. Mutation in a fourth blocks ciliary assembly by an unknown mechanism. These results provide compelling support for the connection between cilia and cystogenesis. Our results also suggest that lesions in genes involved in cilia formation and function are the predominant cause of cystic kidney disease, and that the genes identified here are excellent candidates for novel human PKD genes.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 DevelopmentHome page
N. A. Duldulao, S. Lee, and Z. Sun
Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion
Development, December 1, 2009; 136(23): 4033 - 4042.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
A. M. Ashique, Y. Choe, M. Karlen, S. R. May, K. Phamluong, M. J. Solloway, J. Ericson, and A. S. Peterson
The Rfx4 Transcription Factor Modulates Shh Signaling by Regional Control of Ciliogenesis
Sci. Signal., November 3, 2009; 2(95): ra70 - ra70.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
P. Huang and A. F. Schier
Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia
Development, September 15, 2009; 136(18): 3089 - 3098.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
F. C. Serluca, B. Xu, N. Okabe, K. Baker, S.-Y. Lin, J. Sullivan-Brown, D. J. Konieczkowski, K. M. Jaffe, J. M. Bradner, M. C. Fishman, et al.
Mutations in zebrafish leucine-rich repeat-containing six-like affect cilia motility and result in pronephric cysts, but have variable effects on left-right patterning
Development, May 15, 2009; 136(10): 1621 - 1631.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
L. M. DiBella, A. Park, and Z. Sun
Zebrafish Tsc1 reveals functional interactions between the cilium and the TOR pathway
Hum. Mol. Genet., February 15, 2009; 18(4): 595 - 606.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. I. Ferrante, L. Romio, S. Castro, J. E. Collins, D. A. Goulding, D. L. Stemple, A. S. Woolf, and S. W. Wilson
Convergent extension movements and ciliary function are mediated by ofd1, a zebrafish orthologue of the human oral-facial-digital type 1 syndrome gene
Hum. Mol. Genet., January 15, 2009; 18(2): 289 - 303.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Romaker, M. Puetz, S. Teschner, J. Donauer, M. Geyer, P. Gerke, B. Rumberger, B. Dworniczak, P. Pennekamp, B. Buchholz, et al.
Increased Expression of Secreted Frizzled-Related Protein 4 in Polycystic Kidneys
J. Am. Soc. Nephrol., January 1, 2009; 20(1): 48 - 56.
[Abstract] [Full Text] [PDF]

Home page
 Brief Funct Genomic ProteomicHome page
L.-E. Jao, L. Maddison, W. Chen, and S. M. Burgess
Using retroviruses as a mutagenesis tool to explore the zebrafish genome
Brief Funct Genomic Proteomic, November 1, 2008; 7(6): 427 - 443.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Feng, G. M. Okenka, C.-X. Bai, A. J. Streets, L. J. Newby, B. T. DeChant, L. Tsiokas, T. Obara, and A. C. M. Ong
Identification and Functional Characterization of an N-terminal Oligomerization Domain for Polycystin-2
J. Biol. Chem., October 17, 2008; 283(42): 28471 - 28479.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
M. Kottgen, B. Buchholz, M. A. Garcia-Gonzalez, F. Kotsis, X. Fu, M. Doerken, C. Boehlke, D. Steffl, R. Tauber, T. Wegierski, et al.
TRPP2 and TRPV4 form a polymodal sensory channel complex
J. Cell Biol., August 11, 2008; 182(3): 437 - 447.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
X. Fu, Y. Wang, N. Schetle, H. Gao, M. Putz, G. von Gersdorff, G. Walz, and A. G. Kramer-Zucker
The Subcellular Localization of TRPP2 Modulates Its Function
J. Am. Soc. Nephrol., July 1, 2008; 19(7): 1342 - 1351.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
B. L. Krock and B. D. Perkins
The intraflagellar transport protein IFT57 is required for cilia maintenance and regulates IFT-particle-kinesin-II dissociation in vertebrate photoreceptors
J. Cell Sci., June 1, 2008; 121(11): 1907 - 1915.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
E. van Rooijen, R. H. Giles, E. E. Voest, C. van Rooijen, S. Schulte-Merker, and F. J. van Eeden
LRRC50, a Conserved Ciliary Protein Implicated in Polycystic Kidney Disease
J. Am. Soc. Nephrol., June 1, 2008; 19(6): 1128 - 1138.
[Full Text] [PDF]

Home page
 GeneticsHome page
K. L. Chamberlain, S. H. Miller, and L. R. Keller
Gene Expression Profiling of Flagellar Disassembly in Chlamydomonas reinhardtii
Genetics, May 1, 2008; 179(1): 7 - 19.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
M. B. Lucitt, T. S. Price, A. Pizarro, W. Wu, A. K. Yocum, C. Seiler, M. A. Pack, I. A. Blair, G. A. FitzGerald, and T. Grosser
Analysis of the Zebrafish Proteome during Embryonic Development
Mol. Cell. Proteomics, May 1, 2008; 7(5): 981 - 994.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
C.-C. Tsao and M. A. Gorovsky
Different Effects of Tetrahymena IFT172 Domains on Anterograde and Retrograde Intraflagellar Transport
Mol. Biol. Cell, April 1, 2008; 19(4): 1450 - 1461.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. D. Kinkel, S. C. Eames, M. R. Alonzo, and V. E. Prince
Cdx4 is required in the endoderm to localize the pancreas and limit {beta}-cell number
Development, March 1, 2008; 135(5): 919 - 929.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
Y. Cai and S. Somlo
Too Much of a Good Thing: Does Nek8 Link Polycystic Kidney Disease and Nephronophthisis?
J. Am. Soc. Nephrol., March 1, 2008; 19(3): 418 - 420.
[Full Text] [PDF]

Home page
 J. Cell Sci.Home page
C.-C. Tsao and M. A. Gorovsky
Tetrahymena IFT122A is not essential for cilia assembly but plays a role in returning IFT proteins from the ciliary tip to the cell body
J. Cell Sci., February 15, 2008; 121(4): 428 - 436.
[Abstract] [Full Text] [PDF]

Home page
 NDT PlusHome page
S. Dickinson, S. Carr, J. d. Zoysa, and J. Barratt
Cystic renal disease presenting in pregnancy: a novel presentation of oral-facial-digital syndrome type 1
NDT Plus, February 1, 2008; 1(1): 23 - 25.
[Full Text] [PDF]

Home page
 JCBHome page
K. Huang, D. R. Diener, A. Mitchell, G. J. Pazour, G. B. Witman, and J. L. Rosenbaum
Function and dynamics of PKD2 in Chlamydomonas reinhardtii flagella
J. Cell Biol., November 5, 2007; 179(3): 501 - 514.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
G. Giorgio, M. Alfieri, C. Prattichizzo, A. Zullo, S. Cairo, and B. Franco
Functional Characterization of the OFD1 Protein Reveals a Nuclear Localization and Physical Interaction with Subunits of a Chromatin Remodeling Complex
Mol. Biol. Cell, November 1, 2007; 18(11): 4397 - 4404.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Gouttenoire, U. Valcourt, C. Bougault, E. Aubert-Foucher, E. Arnaud, L. Giraud, and F. Mallein-Gerin
Knockdown of the Intraflagellar Transport Protein IFT46 Stimulates Selective Gene Expression in Mouse Chondrocytes and Affects Early Development in Zebrafish
J. Biol. Chem., October 19, 2007; 282(42): 30960 - 30973.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Tian, R. Kolb, J.-H. Hong, J. Carroll, D. Li, J. You, R. Bronson, M. B. Yaffe, J. Zhou, and T. Benjamin
TAZ Promotes PC2 Degradation through a SCF{beta}-Trcp E3 Ligase Complex
Mol. Cell. Biol., September 15, 2007; 27(18): 6383 - 6395.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. M. McDermott Jr., J. M. Baucom, and A. J. Hudspeth
Analysis and functional evaluation of the hair-cell transcriptome
PNAS, July 10, 2007; 104(28): 11820 - 11825.
[Abstract] [Full Text] [PDF]

Home page
 GENES CELLSHome page
T. Kobayashi, K. Gengyo-Ando, T. Ishihara, I. Katsura, and S. Mitani
IFT-81 and IFT-74 are required for intraflagellar transport in C. elegans
Genes Cells, May 1, 2007; 12(5): 593 - 602.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
J. Schottenfeld, J. Sullivan-Brown, and R. D. Burdine
Zebrafish curly up encodes a Pkd2 ortholog that restricts left-side-specific expression of southpaw
Development, April 15, 2007; 134(8): 1605 - 1615.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
Y. Liu, N. Pathak, A. Kramer-Zucker, and I. A. Drummond
Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros
Development, March 15, 2007; 134(6): 1111 - 1122.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
J. R. Panizzi, J. R. Jessen, I. A. Drummond, and L. Solnica-Krezel
New functions for a vertebrate Rho guanine nucleotide exchange factor in ciliated epithelia
Development, March 1, 2007; 134(5): 921 - 931.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. Varjosalo and J. Taipale
Hedgehog signaling
J. Cell Sci., January 1, 2007; 120(1): 3 - 6.
[Full Text] [PDF]

Home page
 J. Cell Sci.Home page
H. R. Dawe, H. Farr, and K. Gull
Centriole/basal body morphogenesis and migration during ciliogenesis in animal cells
J. Cell Sci., January 1, 2007; 120(1): 7 - 15.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
B. W. Bisgrove and H. J. Yost
The roles of cilia in developmental disorders and disease
Development, November 1, 2006; 133(21): 4131 - 4143.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J. C. Schafer, M. E. Winkelbauer, C. L. Williams, C. J. Haycraft, R. A. Desmond, and B. K. Yoder
IFTA-2 is a conserved cilia protein involved in pathways regulating longevity and dauer formation in Caenorhabditis elegans
J. Cell Sci., October 1, 2006; 119(19): 4088 - 4100.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
T. Obara, S. Mangos, Y. Liu, J. Zhao, S. Wiessner, A. G. Kramer-Zucker, F. Olale, A. F. Schier, and I. A. Drummond
Polycystin-2 Immunolocalization and Function in Zebrafish
J. Am. Soc. Nephrol., October 1, 2006; 17(10): 2706 - 2718.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
I M McGonnell and R C Fowkes
Fishing for gene function - endocrine modelling in the zebrafish.
J. Endocrinol., June 1, 2006; 189(3): 425 - 439.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. J. Streets, D. J. Moon, M. E. Kane, T. Obara, and A. C.M. Ong
Identification of an N-terminal glycogen synthase kinase 3 phosphorylation site which regulates the functional localization of polycystin-2 in vivo and in vitro
Hum. Mol. Genet., May 1, 2006; 15(9): 1465 - 1473.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
L. Geng, D. Okuhara, Z. Yu, X. Tian, Y. Cai, S. Shibazaki, and S. Somlo
Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif
J. Cell Sci., April 1, 2006; 119(7): 1383 - 1395.
[Abstract] [Full Text] [PDF]

Home page
 Brief Funct Genomic ProteomicHome page
A. Amsterdam
Insertional mutagenesis in zebrafish: genes for development, genes for disease
Brief Funct Genomic Proteomic, March 1, 2006; 5(1): 19 - 23.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H.-J. Yen, M. K. Tayeh, R. F. Mullins, E. M. Stone, V. C. Sheffield, and D. C. Slusarski
Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function
Hum. Mol. Genet., March 1, 2006; 15(5): 667 - 677.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
D. Huangfu and K. V. Anderson
Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates
Development, January 1, 2006; 133(1): 3 - 14.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. R. Davenport and B. K. Yoder
An incredible decade for the primary cilium: a look at a once-forgotten organelle
Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1159 - F1169.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
K. C. Sadler, A. Amsterdam, C. Soroka, J. Boyer, and N. Hopkins
A genetic screen in zebrafish identifies the mutants vps18, nf2 and foie gras as models of liver disease
Development, August 1, 2005; 132(15): 3561 - 3572.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. F. Lucker, R. H. Behal, H. Qin, L. C. Siron, W. D. Taggart, J. L. Rosenbaum, and D. G. Cole
Characterization of the Intraflagellar Transport Complex B Core: DIRECT INTERACTION OF THE IFT81 AND IFT74/72 SUBUNITS
J. Biol. Chem., July 29, 2005; 280(30): 27688 - 27696.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
G. J. Pazour, N. Agrin, J. Leszyk, and G. B. Witman
Proteomic analysis of a eukaryotic cilium
J. Cell Biol., July 4, 2005; 170(1): 103 - 113.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
G. W. Morgan, P. W. Denny, S. Vaughan, D. Goulding, T. R. Jeffries, D. F. Smith, K. Gull, and M. C. Field
An Evolutionarily Conserved Coiled-Coil Protein Implicated in Polycystic Kidney Disease Is Involved in Basal Body Duplication and Flagellar Biogenesis in Trypanosoma brucei
Mol. Cell. Biol., May 1, 2005; 25(9): 3774 - 3783.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. M. Gross, B. D. Perkins, A. Amsterdam, A. Egana, T. Darland, J. I. Matsui, S. Sciascia, N. Hopkins, and J. E. Dowling
Identification of Zebrafish Insertional Mutants With Defects in Visual System Development and Function
Genetics, May 1, 2005; 170(1): 245 - 261.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. J. Garcia-Garcia, J. T. Eggenschwiler, T. Caspary, H. L. Alcorn, M. R. Wyler, D. Huangfu, A. S. Rakeman, J. D. Lee, E. H. Feinberg, J. R. Timmer, et al.
Inaugural Article: Analysis of mouse embryonic patterning and morphogenesis by forward genetics
PNAS, April 26, 2005; 102(17): 5913 - 5919.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
A. G. Kramer-Zucker, F. Olale, C. J. Haycraft, B. K. Yoder, A. F. Schier, and I. A. Drummond
Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis
Development, April 15, 2005; 132(8): 1907 - 1921.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
J. J. Essner, J. D. Amack, M. K. Nyholm, E. B. Harris, and H. J. Yost
Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut
Development, March 15, 2005; 132(6): 1247 - 1260.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
V. Stolc, M. P. Samanta, W. Tongprasit, and W. F. Marshall
Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes
PNAS, March 8, 2005; 102(10): 3703 - 3707.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
S. Y. Tay, P. W. Ingham, and S. Roy
A homologue of the Drosophila kinesin-like protein Costal2 regulates Hedgehog signal transduction in the vertebrate embryo
Development, February 15, 2005; 132(4): 625 - 634.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
I. A. Drummond
Kidney Development and Disease in the Zebrafish
J. Am. Soc. Nephrol., February 1, 2005; 16(2): 299 - 304.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
J. Smith
Development in 2005 and beyond
Development, January 1, 2005; 132(1): 1 - 1.
[Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
M. R. Mahjoub, M. Qasim Rasi, and L. M. Quarmby
A NIMA-related Kinase, Fa2p, Localizes to a Novel Site in the Proximal Cilia of Chlamydomonas and Mouse Kidney Cells
Mol. Biol. Cell, November 1, 2004; 15(11): 5172 - 5186.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
G. J. Pazour
Intraflagellar Transport and Cilia-Dependent Renal Disease: The Ciliary Hypothesis of Polycystic Kidney Disease
J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2528 - 2536.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2004