Medaka pp 131-156 | Cite as

Primary Ciliary Dyskinesia in Fish:The Analysis of a Novel Medaka Mutant Kintoun

  • Daisuke Kobayashi
  • Hiroyuki Takeda


Primary ciliary dyskinesia (PCD) is a phenotypically and genetically heterogeneous disorder manifested as dysfunction of motile cilia. Recent investigations using medaka and zebrafish as disease model systems have contributed to the current understanding of the formation and function of motile cilia. This chapter summarizes these data.

We also present our recent investigations of a novel PCD gene, kintoun (ktu), which was discovered in a medaka mutant. This gene was found to be mutated in patients with PCD from two affected families, as well as in the Chlamydomonas pf13 mutant. In the absence of Ktu/PF13, both outer and inner dynein arms are missing or are defective in the axoneme, leading to a loss of motility. Biochemical and immunohistochemical studies show that Ktu/PF13 is one of the long-sought proteins involved in cytoplasmic preassembly of dynein arm complexes before intraflagellar transport loading into the ciliary compartment.


Primary Ciliary Dyskinesia Situs Inversus Central Pair Ciliary Motility Morpholino Antisense Oligonucleotide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Dynein regulatory complex


Inner dynein arm


Intraflagellar transport




Kupffer’s vesicle




Outer dynein arm


Online Mendelian inheritance in man


Primary ciliary dyskinesia


Transmission electron microscopy



The analysis of ktu using the mouse has been done in collaboration with Prof. Yoshinori Watanabe (Institute of Molecular and Cellular Biosciences, University of Tokyo). Mutant screening was supported by the National Institute of Genetics (Mishima, Japan). We are extremely grateful to all the members of our mutant screening team.


  1. Ahsan B, Kobayashi D, Yamada T, Kasahara M, Sasaki S, Saito TL, Nagayasu Y, Doi K, Nakatani Y, Qu W, Jindo T, Shimada A, Naruse K, Toyoda A, Kuroki Y, Fujiyama A, Sasaki T, Shimizu A, Asakawa S, Shimizu N, Hashimoto S, Yang J, Lee Y, Matsushima K, Sugano S, Sakaizumi M, Narita T, Ohishi K, Haga S, Ohta F, Nomoto H, Nogata K, Morishita T, Endo T, Shin IT, Takeda H, Kohara Y, Morishita S (2008) UTGB/medaka: genomic resource database for medaka biology. Nucleic Acids Res 36:D747–D752PubMedCrossRefGoogle Scholar
  2. Amack JD, Yost HJ (2004) The T box transcription factor no tail in ciliated cells controls zebrafish left–right asymmetry. Curr Biol 14:685–690PubMedCrossRefGoogle Scholar
  3. Badano JL, Mitsuma N, Beales PL, Katsanis N (2006) The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet 7:125–148PubMedCrossRefGoogle Scholar
  4. Bartoloni L, Blouin J-L, Pan Y, Gehrig C, Maiti AK, Scamuffa N, Rossier C, Jorissen M, Armengot M, Meeks M, Mitchison HM, Chung EMK, Delozier-Blanchet CD, Craigen WJ, Antonarakis SE (2002) Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Proc Natl Acad Sci USA 99:10282–10286PubMedCrossRefGoogle Scholar
  5. Beales PL, Bland E, Tobin JL, Bacchelli C, Tuysuz B, Hill J, Rix S, Pearson CG, Kai M, Hartley J, Johnson C, Irving M, Elcioglu N, Winey M, Tada M, Scambler PJ (2007) IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy. Nat Genet 39:727–729PubMedCrossRefGoogle Scholar
  6. Bisgrove BW, Yost HJ (2006) The roles of cilia in developmental disorders and disease. Development (Camb) 133:4131–4143CrossRefGoogle Scholar
  7. Bisgrove BW, Snarr BS, Emrazian A, Yost HJ (2005) Polaris and polycystin-2 in dorsal forerunner cells and Kupffer’s vesicle are required for specification of the zebrafish left-right axis. Dev Biol 287:274–288PubMedCrossRefGoogle Scholar
  8. Brody SL, Yan XH, Wuerffel MK, Song SK, Shapiro SD (2000) Ciliogenesis and left-right axis defects in forkhead factor HFH-4-null mice. Am J Respir Cell Mol Biol 23:45–51PubMedGoogle Scholar
  9. Brummett AR, Dumont JN (1978) Kupffer’s vesicle in Fundulus heteroclitus: a scanning and transmission electron microscope study. Tissue Cell 10:11–22PubMedCrossRefGoogle Scholar
  10. Budny B, Chen W, Omran H, Fliegauf M, Tzschach A, Wisniewska M, Jensen LR, Raynaud M, Shoichet SA, Badura M, Lenzner S, Latos-Bielenska A, Ropers HH (2006) A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Hum Genet 120:171–178PubMedCrossRefGoogle Scholar
  11. Cantagrel V, Silhavy JL, Bielas SL, Swistun D, Marsh SE, Bertrand JY, Audollent S, Attie-Bitach T, Holden KR, Dobyns WB, Traver D, Al-Gazali L, Ali BR, Lindner TH, Caspary T, Otto EA, Hildebrandt F, Glass IA, Logan CV, Johnson CA, Bennett C, Brancati F, Valente EM, Woods CG, Gleeson JG (2008) Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome. Am J Hum Genet 83:170–179PubMedCrossRefGoogle Scholar
  12. Castleman VH, Romio L, Chodhari R, Hirst RA, de Castro SCP, Parker KA, Ybot-Gonzalez P, Emes RD, Wilson SW, Wallis C, Johnson CA, Herrera RJ, Rutman A, Dixon M, Shoemark A, Bush A, Hogg C, Gardiner RM, Reish O, Greene NDE, O’Callaghan C, Purton S, Chung EMK, Mitchison HM (2009) Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. Am J Hum Genet 84:197–209PubMedCrossRefGoogle Scholar
  13. Chen J, Knowles HJ, Hebert JL, Hackett BP (1998) Mutation of the mouse hepatocyte nuclear factor/forkhead homologue 4 gene results in an absence of cilia and random left-right asymmetry. J Clin Invest 102:1077–1082PubMedCrossRefGoogle Scholar
  14. Christensen ST, Pedersen LB, Schneider L, Satir P (2007) Sensory cilia and integration of signal transduction in human health and disease. Traffic 8:97–109PubMedCrossRefGoogle Scholar
  15. Colantonio JR, Vermot J, Wu D, Langenbacher AD, Fraser S, Chen J-N, Hill KL (2009) The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear. Nature (Lond) 457:205–209CrossRefGoogle Scholar
  16. Dooley K, Zon LI (2000) Zebrafish: a model system for the study of human disease. Curr Opin Genet Dev 10:252–256PubMedCrossRefGoogle Scholar
  17. Driever W, Solnica-Krezel L, Schier AF, Neuhauss SC, Malicki J, Stemple DL, Stainier DY, Zwartkruis F, Abdelilah S, Rangini Z, Belak J, Boggs C (1996) A genetic screen for mutations affecting embryogenesis in zebrafish. Development (Camb) 123:37–46Google Scholar
  18. Drummond IA (2005) Kidney development and disease in the zebrafish. J Am Soc Nephrol 16:299–304PubMedCrossRefGoogle Scholar
  19. Duriez B, Duquesnoy P, Escudier E, Bridoux A-M, Escalier D, Rayet I, Marcos E, Vojtek A-M, Bercher J-F, Amselem S (2007) A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia. Proc Natl Acad Sci USA 104:3336–3341PubMedCrossRefGoogle Scholar
  20. Essner JJ, Amack JD, Nyholm MK, Harris EB, Yost HJ (2005) 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 (Camb) 132:1247–1260CrossRefGoogle Scholar
  21. Ferrante MI, Giorgio G, Feather SA, Bulfone A, Wright V, Ghiani M, Selicorni A, Gammaro L, Scolari F, Woolf AS, Sylvie O, Bernard L, Malcolm S, Winter R, Ballabio A, Franco B (2001) Identification of the gene for oral-facial-digital type I syndrome. Am J Hum Genet 68:569–576PubMedCrossRefGoogle Scholar
  22. Fliegauf M, Benzing T, Omran H (2007) When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol 8:880–893PubMedCrossRefGoogle Scholar
  23. Fowkes ME, Mitchell DR (1998) The role of preassembled cytoplasmic complexes in assembly of flagellar dynein subunits. Mol Biol Cell 9:2337–2347PubMedGoogle Scholar
  24. Freshour J, Yokoyama R, Mitchell DR (2007) Chlamydomonas flagellar outer row dynein assembly protein Oda7 interacts with both outer row and I1 inner row dyneins. J Biol Chem 282:5404–5412PubMedCrossRefGoogle Scholar
  25. Furutani-Seiki M, Sasado T, Morinaga C, Suwa H, Niwa K, Yoda H, Deguchi T, Hirose Y, Yasuoka A, Henrich T, Watanabe T, Iwanami N, Kitagawa D, Saito K, Asaka S, Osakada M, Kunimatsu S, Momoi A, Elmasri H, Winkler C, Ramialison M, Loosli F, Quiring R, Carl M, Grabher C, Winkler S, Del Bene F, Shinomiya A, Kota Y, Yamanaka T, Okamoto Y, Takahashi K, Todo T, Abe K, Takahama Y, Tanaka M, Mitani H, Katada T, Nishina H, Nakajima N, Wittbrodt J, Kondoh H (2004) A systematic genome-wide screen for mutations affecting organogenesis in medaka, Oryzias latipes. Mech Dev 121:647–658PubMedCrossRefGoogle Scholar
  26. Gerdes JM, Davis EE, Katsanis N (2009) The vertebrate primary cilium in development, homeostasis, and disease. Cell 137:32–45PubMedCrossRefGoogle Scholar
  27. Gonzales FA, Zanchin NI, Luz JS, Oliveira CC (2005) Characterization of Saccharomyces cerevisiae Nop17p, a novel Nop58p-interacting protein that is involved in Pre-rRNA processing. J Mol Biol 346:437–455PubMedCrossRefGoogle Scholar
  28. Gorden NT, Arts HH, Parisi MA, Coene KL, Letteboer SJ, van Beersum SE, Mans DA, Hikida A, Eckert M, Knutzen D, Alswaid AF, Ozyurek H, Dibooglu S, Otto EA, Liu Y, Davis EE, Hutter CM, Bammler TK, Farin FM, Dorschner M, Topçu M, Zackai EH, Rosenthal P, Owens KN, Katsanis N, Vincent JB, Hildebrandt F, Rubel EW, Raible DW, Knoers NV, Chance PF, Roepman R, Moens CB, Glass IA, Doherty D(2008) CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290. Am J Hum Genet 83:559–571Google Scholar
  29. Haffter P, Granato M, Brand M, Mullins MC, Hammerschmidt M, Kane DA, Odenthal J, van Eeden FJ, Jiang YJ, Heisenberg CP, Kelsh RN, Furutani-Seiki M, Vogelsang E, Beuchle D, Schach U, Fabian C, Nusslein-Volhard C (1996) The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development (Camb) 123:1–36Google Scholar
  30. Hagiwara H, Ohwada N, Takata K (2004) Cell biology of normal and abnormal ciliogenesis in the ciliated epithelium. Int Rev Cytol 234:101–141PubMedCrossRefGoogle Scholar
  31. Hirokawa N, Tanaka Y, Okada Y, Takeda S (2006) Nodal flow and the generation of left-right asymmetry. Cell 125:33–45PubMedCrossRefGoogle Scholar
  32. Hojo M, Takashima S, Kobayashi D, Sumeragi A, Shimada A, Tsukahara T, Yokoi H, Narita T, Jindo T, Kage T, Kitagawa T, Kimura T, Sekimizu K, Miyake A, Setiamarga D, Murakami R, Tsuda S, Ooki S, Kakihara K, Naruse K, Takeda H (2007) Right-elevated expression of charon is regulated by fluid flow in medaka Kupffer’s vesicle. Dev Growth Differ 49:395–405PubMedCrossRefGoogle Scholar
  33. Huang B, Piperno G, Luck DJ (1979) Paralyzed flagella mutants of Chlamydomonas reinhardtii. Defective for axonemal doublet microtubule arms. J Biol Chem 254:3091–3099PubMedGoogle Scholar
  34. Hutchings NR, Donelson JE, Hill KL (2002) Trypanin is a cytoskeletal linker protein and is required for cell motility in African trypanosomes. J Cell Biol 156:867–877PubMedCrossRefGoogle Scholar
  35. Ibanez-Tallon I, Heintz N, Omran H (2003) To beat or not to beat: roles of cilia in development and disease. Hum Mol Genet 12:R27–R35PubMedCrossRefGoogle Scholar
  36. Kamiya R (1988) Mutations at twelve independent loci result in absence of outer dynein arms in Chlamydomonas reinhardtii. J Cell Biol 107:2253–2258PubMedCrossRefGoogle Scholar
  37. Kamiya R (2002) Functional diversity of axonemal dyneins as studied in Chlamydomonas mutants. Int Rev Cytol 219:115–155PubMedCrossRefGoogle Scholar
  38. Kasahara M, Naruse K, Sasaki S, Nakatani Y, Qu W, Ahsan B, Yamada T, Nagayasu Y, Doi K, Kasai Y, Jindo T, Kobayashi D, Shimada A, Toyoda A, Kuroki Y, Fujiyama A, Sasaki T, Shimizu A, Asakawa S, Shimizu N, Hashimoto S-i, Yang J, Lee Y, Matsushima K, Sugano S, Sakaizumi M, Narita T, Ohishi K, Haga S, Ohta F, Nomoto H, Nogata K, Morishita T, Endo T, Shin-I T, Takeda H, Morishita S, Kohara Y (2007) The medaka draft genome and insights into vertebrate genome evolution. Nature (Lond) 447:714–719CrossRefGoogle Scholar
  39. Kishimoto N, Cao Y, Park A, Sun Z (2008) Cystic kidney gene seahorse regulates cilia-mediated processes and Wnt pathways. Dev Cell 14:954–961PubMedCrossRefGoogle Scholar
  40. Kobayashi D, Takeda H (2008) Medaka genome project. Brief Funct Genomic Proteomic 7:415–426PubMedCrossRefGoogle Scholar
  41. Kramer-Zucker AG, Olale F, Haycraft CJ, Yoder BK, Schier AF, Drummond IA (2005) Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer’s vesicle is required for normal organogenesis. Development (Camb) 132:1907–1921CrossRefGoogle Scholar
  42. Loges NT, Olbrich H, Fenske L, Mussaffi H, Horvath J, Fliegauf M, Kuhl H, Baktai G, Peterffy E, Chodhari R, Chung EMK, Rutman A, O’Callaghan C, Blau H, Tiszlavicz L, Voelkel K, Witt M, Zietkiewicz E, Neesen J, Reinhardt R, Mitchison HM, Omran H (2008) DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer dynein arm. Am J Hum Genet 83:547–558PubMedCrossRefGoogle Scholar
  43. Low SH, Vasanth S, Larson CH, Mukherjee S, Sharma N, Kinter MT, Kane ME, Obara T, Weimbs T (2006) Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease. Dev Cell 10:57–69PubMedCrossRefGoogle Scholar
  44. Mochizuki E, Fukuta K, Tada T, Harada T, Watanabe N, Matsuo S, Hashimoto H, Ozato K, Wakamatsu Y (2005) Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant. Kidney Int 68:23–34PubMedCrossRefGoogle Scholar
  45. Moore A, Escudier E, Roger G, Tamalet A, Pelosse B, Marlin S, Clement A, Geremek M, Delaisi B, Bridoux AM, Coste A, Witt M, Duriez B, Amselem S (2006) RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. J Med Genet 43:326–333PubMedCrossRefGoogle Scholar
  46. Nasevicius A, Ekker SC (2000) Effective targeted gene ‘knockdown’ in zebrafish. Nat Genet 26:216–220PubMedCrossRefGoogle Scholar
  47. Okada Y, Nonaka S, Tanaka Y, Saijoh Y, Hamada H, Hirokawa N (1999) Abnormal nodal flow precedes situs inversus in iv and inv mice. Mol Cell 4:459–468PubMedCrossRefGoogle Scholar
  48. Okada Y, Takeda S, Tanaka Y, Belmonte J-CI, Hirokawa N (2005) Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination. Cell 121:633–644PubMedCrossRefGoogle Scholar
  49. Olbrich H, Haffner K, Kispert A, Volkel A, Volz A, Sasmaz G, Reinhardt R, Hennig S, Lehrach H, Konietzko N, Zariwala M, Noone PG, Knowles M, Mitchison HM, Meeks M, Chung EMK, Hildebrandt F, Sudbrak R, Omran H (2002) Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nat Genet 30:143–144PubMedCrossRefGoogle Scholar
  50. Omran H, Haffner K, Volkel A, Kuehr J, Ketelsen U-P, Ross U-H, Konietzko N, Wienker T, Brandis M, Hildebrandt F (2000) Homozygosity mapping of a gene locus for primary ciliary dyskinesia on chromosome 5p and identification of the heavy dynein chain DNAH5 as a candidate gene. Am J Respir Cell Mol Biol 23:696–702PubMedGoogle Scholar
  51. Omran H, Kobayashi D, Olbrich H, Tsukahara T, Loges NT, Hagiwara H, Zhang Q, Leblond G, O’Toole E, Hara C, Mizuno H, Kawano H, Fliegauf M, Yagi T, Koshida S, Miyawaki A, Zentgraf H, Seithe H, Reinhardt R, Watanabe Y, Kamiya R, Mitchell DR, Takeda H (2008) Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins. Nature (Lond) 456:611–616CrossRefGoogle Scholar
  52. Otto EA, Schermer B, Obara T, O’Toole JF, Hiller KS, Mueller AM, Ruf RG, Hoefele J, Beekmann F, Landau D, Foreman JW, Goodship JA, Strachan T, Kispert A, Wolf MT, Gagnadoux MF, Nivet H, Antignac C, Walz G, Drummond IA, Benzing T, Hildebrandt F (2003) Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat Genet 34:413–420PubMedCrossRefGoogle Scholar
  53. Pennarun G, Escudier E, Chapelin C, Bridoux AM, Cacheux V, Roger G, Clement A, Goossens M, Amselem S, Duriez B (1999) Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. Am J Hum Genet 65:1508–1519PubMedCrossRefGoogle Scholar
  54. Rosenbaum JL, Witman GB (2002) Intraflagellar transport. Nat Rev Mol Cell Biol 3:813–825PubMedCrossRefGoogle Scholar
  55. Rupp G, Porter ME (2003) A subunit of the dynein regulatory complex in Chlamydomonas is a homologue of a growth arrest-specific gene product. J Cell Biol 162:47–57PubMedCrossRefGoogle Scholar
  56. Sarmah B, Latimer AJ, Appel B, Wente SR (2005) Inositol polyphosphates regulate zebrafish left-right asymmetry. Dev Cell 9:133PubMedCrossRefGoogle Scholar
  57. Sarmah B, Winfrey VP, Olson GE, Appel B, Wente SR (2007) A role for the inositol kinase Ipk1 in ciliary beating and length maintenance. Proc Natl Acad Sci USA 104:19843–19848PubMedCrossRefGoogle Scholar
  58. Satir P, Christensen ST (2007) Overview of structure and function of mammalian cilia. Annu Rev Physiol 69:377–400PubMedCrossRefGoogle Scholar
  59. Sayer JA, Otto EA, O’Toole JF, Nurnberg G, Kennedy MA, Becker C, Hennies HC, Helou J, Attanasio M, Fausett BV, Utsch B, Khanna H, Liu Y, Drummond I, Kawakami I, Kusakabe T, Tsuda M, Ma L, Lee H, Larson RG, Allen SJ, Wilkinson CJ, Nigg EA, Shou C, Lillo C, Williams DS, Hoppe B, Kemper MJ, Neuhaus T, Parisi MA, Glass IA, Petry M, Kispert A, Gloy J, Ganner A, Walz G, Zhu X, Goldman D, Nurnberg P, Swaroop A, Leroux MR, Hildebrandt F (2006) The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat Genet 38:674–681PubMedCrossRefGoogle Scholar
  60. Schafer T, Putz M, Lienkamp S, Ganner A, Bergbreiter A, Ramachandran H, Gieloff V, Gerner M, Mattonet C, Czarnecki PG, Sayer JA, Otto EA, Hildebrandt F, Kramer-Zucker A, Walz G (2008) Genetic and physical interaction between the NPHP5 and NPHP6 gene products. Hum Mol Genet 17:3655–3662PubMedCrossRefGoogle Scholar
  61. Schottenfeld J, Sullivan-Brown J, Burdine RD(2007) Zebrafish curly up encodes a Pkd2 ortholog that restricts left-side-specific expression of southpaw. Development (Camb) 134:1605–1615Google Scholar
  62. Schweickert A, Weber T, Beyer T, Vick P, Bogusch S, Feistel K, Blum M (2007) Cilia-driven leftward flow determines laterality in Xenopus. Curr Biol 17:60–66PubMedCrossRefGoogle Scholar
  63. Serluca FC, Xu B, Okabe N, Baker K, Lin S-Y, Sullivan-Brown J, Konieczkowski DJ, Jaffe KM, Bradner JM, Fishman MC, Burdine RD (2009) 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 (Camb) 136:1621–1631CrossRefGoogle Scholar
  64. Shu X, Huang J, Dong Y, Choi J, Langenbacher A, Chen J-N (2007) Na, K-ATPase α2 and Ncx4a regulate zebrafish left–right patterning. Development (Camb) 134:1921–1930CrossRefGoogle Scholar
  65. Stannard W, Rutman A, Wallis C, O’Callaghan C (2004) Central microtubular agenesis causing primary ciliary dyskinesia. Am J Respir Crit Care Med 169:634–637PubMedCrossRefGoogle Scholar
  66. Streets AJ, Moon DJ, Kane ME, Obara T, Ong ACM (2006) 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 15:1465–1473PubMedCrossRefGoogle Scholar
  67. Stubbs JL, Oishi I, Izpisua Belmonte JC, Kintner C (2008) The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos. Nat Genet 40:1454–1460PubMedCrossRefGoogle Scholar
  68. Sullivan-Brown J, Schottenfeld J, Okabe N, Hostetter CL, Serluca FC, Thiberge SY, Burdine RD (2008) Zebrafish mutations affecting cilia motility share similar cystic phenotypes and suggest a mechanism of cyst formation that differs from pkd2 morphants. Dev Biol 314:261–275PubMedCrossRefGoogle Scholar
  69. Sun Z, Amsterdam A, Pazour GJ, Cole DG, Miller MS, Hopkins N (2004) A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney. Development (Camb) 131:4085–4093CrossRefGoogle Scholar
  70. Takeda H (2008) Draft genome of the medaka fish: a comprehensive resource for medaka developmental genetics and vertebrate evolutionary biology. Dev Growth Differ 50(suppl 1):S157–S166PubMedCrossRefGoogle Scholar
  71. Tobin JL, Beales PL (2008) Restoration of renal function in zebrafish models of ciliopathies. Pediatr Nephrol 23:2095–2099PubMedCrossRefGoogle Scholar
  72. van Rooijen E, Giles RH, Voest EE, van Rooijen C, Schulte-Merker S, van Eeden FJ (2008) LRRC50, a conserved ciliary protein implicated in polycystic kidney disease. J Am Soc Nephrol 19:1128–1138PubMedCrossRefGoogle Scholar
  73. Wessely O, Obara T (2008) Fish and frogs: models for vertebrate cilia signaling. Front Biosci 13:1866–1880PubMedCrossRefGoogle Scholar
  74. Wilson CW, Nguyen CT, Chen M-H, Yang J-H, Gacayan R, Huang J, Chen J-N, Chuang P-T (2009) Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis. Nature (Lond) 459:98–102CrossRefGoogle Scholar
  75. Yang P, Diener DR, Yang C, Kohno T, Pazour GJ, Dienes JM, Agrin NS, King SM, Sale WS, Kamiya R, Rosenbaum JL, Witman GB (2006) Radial spoke proteins of Chlamydomonas flagella. J Cell Sci 119:1165–1174PubMedCrossRefGoogle Scholar
  76. Yokoi H, Shimada A, Carl M, Takashima S, Kobayashi D, Narita T, Jindo T, Kimura T, Kitagawa T, Kage T, Sawada A, Naruse K, Asakawa S, Shimizu N, Mitani H, Shima A, Tsutsumi M, Hori H, Wittbrodt J, Saga Y, Ishikawa Y, Araki K, Takeda H (2007) Mutant analyses reveal different functions of fgfr1 in medaka and zebrafish despite conserved ligand-receptor relationships. Dev Biol 304:326PubMedCrossRefGoogle Scholar
  77. Yu X, Ng CP, Habacher H, Roy S (2008) Foxj1 transcription factors are master regulators of the motile ciliogenic program. Nat Genet 40:1445–1453PubMedCrossRefGoogle Scholar
  78. Zariwala MA, Knowles MR, Omran H (2007) Genetic defects in ciliary structure and function. Annu Rev Physiol 69:423–450PubMedCrossRefGoogle Scholar
  79. Zhao R, Davey M, Hsu YC, Kaplanek P, Tong A, Parsons AB, Krogan N, Cagney G, Mai D, Greenblatt J, Boone C, Emili A, Houry WA (2005) Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone. Cell 120:715–727PubMedCrossRefGoogle Scholar
  80. Zon LI, Peterson RT (2005) In vivo drug discovery in the zebrafish. Nat Rev Drug Discov 4:35–44PubMedCrossRefGoogle Scholar

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© Springer 2011

Authors and Affiliations

  1. 1.Department of Anatomy and Developmental BiologyGraduate School of Medical Science, Kyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of Biological SciencesGraduate School of Science, The University of Tokyo,TokyoJapan

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