|
|
|
Cilia in cell signaling and human disorders |
| Neil A. Duldulao,Jade Li,Zhaoxia Sun, |
| Department of Genetics,
Yale University School of Medicine, 333 Cedar St., SHM I-329A, New
Haven, CT 06520, USA; |
|
|
|
|
Abstract One of the most widespread cellular organelles in nature is cilium, which is found in many unicellular and multicellular organisms. Formerly thought to be a mostly vestigial organelle, the cilium has been discovered in the past several decades to play critical motile and sensory roles involved in normal organogenesis during development. The role of cilia has also been implicated in an ever increasing array of seemingly unrelated human diseases, including blindness, kidney cysts, neural tube defects and obesity. In this article we review some of the recent developments in research on cilia, and how defects in ciliogenesis and function can give rise to developmental disorders and disease.
|
| Keywords
cilia
ciliogenesis
ciliopathy
model organisms
|
|
Issue Date: 01 August 2010
|
|
|
Arts, H.H., Doherty, D., van Beersum, S.E., Parisi, M.A., Letteboer, S.J., Gorden, N.T., Peters, T.A., M?rker, T., Voesenek, K., Kartono, A., et al. (2007). Mutations in the gene encodingthe basal body protein RPGRIP1L, a nephrocystin-4 interactor, causeJoubert syndrome. Nat Genet 39, 882–888.
doi: 10.1038/ng2069
|
|
Asleson, C.M., and Lefebvre, P.A. (1998). Genetic analysis of flagellar length control in Chlamydomonasreinhardtii: a new long-flagella locus and extragenic suppressor mutations. Genetics 148, 693–702.
|
|
Avidor-Reiss, T. (2010). The cellular and developmental programconnecting the centrosome and cilium duplication cycle. Semin Cell Dev Biol 21, 139–141.
doi: 10.1016/j.semcdb.2010.01.014
|
|
Baala, L., Romano, S., Khaddour, R., Saunier, S., Smith, U.M., Audollent, S., Ozilou, C., Faivre, L., Laurent, N., Foliguet, B., et al. (2007). The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome. Am J Hum Genet 80, 186–194.
doi: 10.1086/510499
|
|
Bai, C.B., Auerbach, W., Lee, J.S., Stephen, D., and Joyner, A.L. (2002). Gli2, but not Gli1, is required for initial Shh signalingand ectopic activation of the Shh pathway. Development 129, 4753–4761.
|
|
Barr, M.M., and Sternberg, P.W. (1999). A polycystic kidney-disease gene homologue requiredfor male mating behaviour in C. elegans. Nature 401, 386–389.
doi: 10.1038/43913
|
|
Barr, M.M., DeModena, J., Braun, D., Nguyen, C.Q., Hall, D.H., and Sternberg, P.W. (2001). The Caenorhabditis elegans autosomal dominant polycystic kidney diseasegene homologs lov-1 and pkd-2 act in the same pathway. Curr Biol 11, 1341–1346.
doi: 10.1016/S0960-9822(01)00423-7
|
|
Barsel, S.E., Wexler, D.E., and Lefebvre, P.A. (1988). Genetic analysis of long-flagella mutants of Chlamydomonas reinhardtii. Genetics 118, 637–648.
|
|
Berbari, N.F., Lewis, J.S., Bishop, G.A., Askwith, C.C., and Mykytyn, K. (2008). Bardet-Biedl syndrome proteins are required for thelocalization of G protein-coupled receptors to primary cilia. Proc Natl Acad Sci U S A 105, 4242–4246.
doi: 10.1073/pnas.0711027105
|
|
Berman, S.A., Wilson, N.F., Haas, N.A., and Lefebvre, P.A. (2003). A novel MAP kinase regulates flagellar length in Chlamydomonas. Curr Biol 13, 1145–1149.
doi: 10.1016/S0960-9822(03)00415-9
|
|
Bielas, S.L., Silhavy, J.L., Brancati, F., Kisseleva, M.V., Al-Gazali, L., Sztriha, L., Bayoumi, R.A., Zaki, M.S., Abdel-Aleem, A., Rosti, R.O., et al. (2009a). Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositolsignaling to the ciliopathies. Nat Genet 41, 1032-1036.
|
|
Bingham, C., Bulman, M.P., Ellard, S., Allen, L.I., Lipkin, G.W., Hoff, W.G., Woolf, A.S., Rizzoni, G., Novelli, G., Nicholls, A.J., et al. (2001). Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplasticglomerulocystic kidney disease. Am J Hum Genet 68, 219–224.
doi: 10.1086/316945
|
|
Cantagrel, V., Silhavy, J.L., Bielas, S.L., Swistun, D., Marsh, S.E., Bertrand, J.Y., Audollent, S., Attié-Bitach, T., Holden, K.R., Dobyns, W.B., et al, and the International Joubert Syndrome Related Disorders Study Group. (2008). Mutations in the cilia gene ARL13B lead to the classical form ofJoubert syndrome. Am J Hum Genet 83, 170–179.
doi: 10.1016/j.ajhg.2008.06.023
|
|
Carruthers, S., and Stemple, D.L. (2006). Genetic and genomic prospects for Xenopus tropicalisresearch. Semin Cell Dev Biol 17, 146–153.
doi: 10.1016/j.semcdb.2005.11.009
|
|
Caspary, T., Larkins, C.E., and Anderson, K.V. (2007). The graded response to Sonic Hedgehog depends on cilia architecture. Dev Cell 12, 767–778.
doi: 10.1016/j.devcel.2007.03.004
|
|
Chang, B., Khanna, H., Hawes, N., Jimeno, D., He, S., Lillo, C., Parapuram, S.K., Cheng, H., Scott, A., Hurd, R.E., et al. (2006). In-frame deletion in a novel centrosomal/ciliary proteinCEP290/NPHP6 perturbs its interaction with RPGR and results in early-onsetretinal degeneration in the rd16 mouse. Hum Mol Genet 15, 1847–1857.
doi: 10.1093/hmg/ddl107
|
|
Coene, K.L., Roepman, R., Doherty, D., Afroze, B., Kroes, H.Y., Letteboer, S.J., Ngu, L.H., Budny, B., van Wijk, E., Gorden, N.T., et al. (2009). OFD1 is mutated in X-linkedJoubert syndrome and interacts with LCA5-encoded lebercilin. Am J Hum Genet 85, 465–481.
doi: 10.1016/j.ajhg.2009.09.002
|
|
Cole, D.G., Diener, D.R., Himelblau, A.L., Beech, P.L., Fuster, J.C., and Rosenbaum, J.L. (1998). Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particlescontain proteins required for ciliary assembly in Caenorhabditis eleganssensory neurons. J Cell Biol 141, 993–1008.
doi: 10.1083/jcb.141.4.993
|
|
Collet, J., Spike, C.A., Lundquist, E.A., Shaw, J.E., and Herman, R.K. (1998). Analysis of osm-6, a gene that affects sensory ciliumstructure and sensory neuron function in Caenorhabditis elegans. Genetics 148, 187–200.
|
|
Corbit, K.C., Aanstad, P., Singla, V., Norman, A.R., Stainier, D.Y., and Reiter, J.F. (2005). Vertebrate Smoothened functions at the primary cilium. Nature 437, 1018–1021.
doi: 10.1038/nature04117
|
|
Corbit, K.C., Shyer, A.E., Dowdle, W.E., Gaulden, J., Singla, V., Chen, M.H., Chuang, P.T., Reiter, J.F. (2008). Kif3a constrains beta-catenin-dependent Wnt signallingthrough dual ciliary and non-ciliary mechanisms. Nat Cell Biol 10, 70–76.
doi: 10.1038/ncb1670
|
|
Cortellino, S., Wang, C., Wang, B., Bassi, M.R., Caretti, E., Champeval, D., Calmont, A., Jarnik, M., Burch, J., Zaret, K.S., et al. (2009). Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivationof the mouse complex A intraflagellar transport gene Ift122/Wdr10,partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol 325, 225–237.
doi: 10.1016/j.ydbio.2008.10.020
|
|
Dahmane, N., and Ruiz i Altaba, A. (1999). Sonic hedgehog regulates the growth and patterning ofthe cerebellum. Development 126, 3089–3100.
|
|
Davenport, J.R., Watts, A.J., Roper, V.C., Croyle, M.J., van Groen, T., Wyss, J.M., Nagy, T.R., Kesterson, R.A., and Yoder, B.K. (2007). Disruption of intraflagellar transport in adult mice leads to obesity and slow-onsetcystic kidney disease. Curr Biol 17, 1586–1594.
doi: 10.1016/j.cub.2007.08.034
|
|
Dawe, H.R., Smith, U.M., Cullinane, A.R., Gerrelli, D., Cox, P., Badano, J.L., Blair-Reid, S., Sriram, N., Katsanis, N., Attie-Bitach, T., et al. (2007). The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required forprimary cilium formation. Hum Mol Genet 16, 173–186.
doi: 10.1093/hmg/ddl459
|
|
Deane, J.A., Cole, D.G., Seeley, E.S., Diener, D.R., and Rosenbaum, J.L. (2001). Localization of intraflagellar transport protein IFT52identifies basal body transitional fibers as the docking site forIFT particles. Curr Biol 11, 1586–1590.
doi: 10.1016/S0960-9822(01)00484-5
|
|
Deblandre, G.A., Wettstein, D.A., Koyano-Nakagawa, N., and Kintner, C. (1999). A two-step mechanism generates the spacing pattern of the ciliated cells in the skin ofXenopus embryos. Development 126, 4715–4728.
|
|
Delous, M., Baala, L., Salomon, R., Laclef, C., Vierkotten, J., Tory, K., Golzio, C., Lacoste, T., Besse, L., Ozilou, C., et al. (2007). The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome typeB) and Meckel syndrome. Nat Genet 39, 875–881.
doi: 10.1038/ng2039
|
|
Denef, N., Neubüser, D., Perez, L., and Cohen, S.M. (2000). Hedgehog induces opposite changes in turnover and subcellular localization of patchedand smoothened. Cell 102, 521–531.
doi: 10.1016/S0092-8674(00)00056-8
|
|
Dixon-Salazar, T., Silhavy, J.L., Marsh, S.E., Louie, C.M., Scott, L.C., Gururaj, A., Al-Gazali, L., Al-Tawari, A.A., Kayserili, H., Sztriha, L., et al. (2004). Mutations in the AHI1 gene,encoding jouberin, cause Joubert syndrome with cortical polymicrogyria. Am J Hum Genet 75, 979–987.
doi: 10.1086/425985
|
|
Doherty, D. (2009). Joubert syndrome: insights intobrain development, cilium biology, and complex disease. Semin Pediatr Neurol 16, 143–154.
doi: 10.1016/j.spen.2009.06.002
|
|
Donaldson, J.C., Dempsey, P.J., Reddy, S., Bouton, A.H., Coffey, R.J., and Hanks, S.K. (2000). Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteinslocalize to cell-cell contacts of polarized epithelial cells. Exp Cell Res 256, 168–178.
doi: 10.1006/excr.2000.4822
|
|
Donaldson, J.C., Dise, R.S., Ritchie, M.D., and Hanks, S.K. (2002). Nephrocystin-conserved domains involved in targeting to epithelial cell-cell junctions, interactionwith filamins, and establishing cell polarity. J Biol Chem 277, 29028–29035.
doi: 10.1074/jbc.M111697200
|
|
Doyon, Y., McCammon, J.M., Miller, J.C., Faraji, F., Ngo, C., Katibah, G.E., Amora, R., Hocking, T.D., Zhang, L., Rebar, E.J., et al. (2008). Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26, 702–708.
doi: 10.1038/nbt1409
|
|
Duldulao, N.A., Lee, S., and Sun, Z. (2009). Cilia localizationis essential for in vivo functions of the Joubert syndrome proteinArl13b/Scorpion. Development 136, 4033–4042.
doi: 10.1242/dev.036350
|
|
Edvardson, S., Shaag, A., Zenvirt, S., Erlich, Y., Hannon, G.J., Shanske, A.L., Gomori, J.M., Ekstein, J., and Elpeleg, O. (2010). Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216mutation. Am J Hum Genet 86, 93–97.
doi: 10.1016/j.ajhg.2009.12.007
|
|
Eggenschwiler, J.T., Anderson, K.V. (2007). Cilia and developmental signaling. Annu Rev Cell Dev Biol 23, 345–373.
doi: 10.1146/annurev.cellbio.23.090506.123249
|
|
Ekker, S.C. (2000). Morphants: a new systematic vertebratefunctional genomics approach. Yeast 17, 302–306.
doi: 10.1002/1097-0061(200012)17:4<302::AID-YEA53>3.0.CO;2-#
|
|
Ferland, R.J., Eyaid, W., Collura, R.V., Tully, L.D., Hill, R.S., Al-Nouri, D., Al-Rumayyan, A., Topcu, M., Gascon, G., Bodell, A., et al. (2004). Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nat Genet 36, 1008–1013.
doi: 10.1038/ng1419
|
|
Ferrante, M.I., Zullo, A., Barra, A., Bimonte, S., Messaddeq, N., Studer, M., Dollé, P., and Franco, B. (2006). Oral-facial-digital type I protein is required for primarycilia formation and left-right axis specification. Nat Genet 38, 112–117.
doi: 10.1038/ng1684
|
|
Fliegauf, M., Horvath, J., von Schnakenburg, C., Olbrich, H., Müller, D., Thumfart, J., Schermer, B., Pazour, G.J., Neumann, H.P., Zentgraf, H., et al. (2006). Nephrocystin specifically localizes to the transition zone of renal and respiratory cilia andphotoreceptor connecting cilia. J Am Soc Nephrol 17, 2424–2433.
doi: 10.1681/ASN.2005121351
|
|
Fluss, J., Blaser, S., Chitayat, D., Akoury, H., Glanc, P., Skidmore, M., and Raybaud, C. (2006). Molar tooth sign in fetal brain magnetic resonance imaging leading to the prenataldiagnosis of Joubert syndrome and related disorders. J Child Neurol 21, 320–324.
doi: 10.1177/08830738060210041001
|
|
Foley, J.E., Yeh, J.R., Maeder, M.L., Reyon, D., Sander, J.D., Peterson, R.T., Joung, J.K., and Raible, D.W. (2009). Rapid mutation of endogenous zebrafish genes using zincfinger nucleases made by Oligomerized Pool ENgineering (OPEN). PLoS ONE 4, e4348.
doi: 10.1371/journal.pone.0004348
|
|
Frank, V., den Hollander, A.I., Brüchle, N.O., Zonneveld, M.N., Nürnberg, G., Becker, C., Du Bois, G., Kendziorra, H., Roosing, S., Senderek, J., et al. (2008). Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome. Hum Mutat 29, 45–52.
doi: 10.1002/humu.20614
|
|
Gerdes, J.M., Liu, Y., Zaghloul, N.A., Leitch, C.C., Lawson, S.S., Kato, M., Beachy, P.A., Beales, P.L., DeMartino, G.N., Fisher, S., et al. (2007). Disruption of the basal body compromises proteasomal function and perturbs intracellular Wntresponse. Nat Genet 39, 1350–1360.
doi: 10.1038/ng.2007.12
|
|
Gorden, N.T., Arts, H.H., Parisi, M.A., Coene, K.L., Letteboer, S.J., van Beersum, S.E., Mans, D.A., Hikida, A., Eckert, M., Knutzen, D., et al. (2008). CC2D2A is mutated in Joubertsyndrome and interacts with the ciliopathy-associated basal body proteinCEP290. Am J Hum Genet 83, 559–571.
doi: 10.1016/j.ajhg.2008.10.002
|
|
H?ndel, M., Schulz, S., Stanarius, A., Schreff, M., Erdtmann-Vourliotis, M., Schmidt, H., Wolf, G., and H?llt, V. (1999). Selective targeting of somatostatin receptor 3 to neuronalcilia. Neuroscience 89, 909–926.
doi: 10.1016/S0306-4522(98)00354-6
|
|
Haycraft, C.J., Banizs, B., Aydin-Son, Y., Zhang, Q., Michaud, E.J., and Yoder, B.K. (2005). Gli2 and Gli3 localize to cilia and require the intraflagellar transportprotein polaris for processing and function. PLoS Genet 1, e53.
doi: 10.1371/journal.pgen.0010053
|
|
Haycraft, C.J., Zhang, Q., Song, B., Jackson, W.S., Detloff, P.J., Serra, R., and Yoder, B.K. (2007). Intraflagellar transport is essential for endochondral bone formation. Development 134, 307–316.
doi: 10.1242/dev.02732
|
|
Hayes, J.M., Kim, S.K., Abitua, P.B., Park, T.J., Herrington, E.R., Kitayama, A., Grow, M.W., Ueno, N., and Wallingford, J.B. (2007). Identification of novel ciliogenesis factors using a new in vivo model for mucociliaryepithelial development. Dev Biol 312, 115–130.
doi: 10.1016/j.ydbio.2007.09.031
|
|
Hildebrandt, F., Otto, E., Rensing, C., Nothwang, H.G., Vollmer, M., Adolphs, J., Hanusch, H., and Brandis, M. (1997). A novel gene encoding an SH3 domain protein is mutated in nephronophthisistype 1. Nat Genet 17, 149–153.
doi: 10.1038/ng1097-149
|
|
Hildebrandt, F., Attanasio, M., and Otto, E. (2009). Nephronophthisis: disease mechanisms of a ciliopathy. J Am Soc Nephrol 20, 23–35.
doi: 10.1681/ASN.2008050456
|
|
Hirsch, N., Zimmerman, L.B., and Grainger, R.M. (2002). Xenopus, the next generation: X. tropicalis genetics and genomics. Dev Dyn 225, 422–433.
doi: 10.1002/dvdy.10178
|
|
Huang, P., and Schier, A.F. (2009). Dampened Hedgehog signaling but normal Wnt signalingin zebrafish without cilia. Development 136, 3089–3098.
doi: 10.1242/dev.041343
|
|
Huangfu, D., and Anderson, K.V. (2006). Signaling from Smo to Ci/Gli: conservation and divergenceof Hedgehog pathways from Drosophila to vertebrates. Development 133, 3–14.
doi: 10.1242/dev.02169
|
|
Huangfu, D., Liu, A., Rakeman, A.S., Murcia, N.S., Niswander, L., and Anderson, K.V. (2003). Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426, 83–87.
doi: 10.1038/nature02061
|
|
Iba?ez-Tallon, I., Pagenstecher, A., Fliegauf, M., Olbrich, H., Kispert, A., Ketelsen, U.P., North, A., Heintz, N., and Omran, H. (2004). Dysfunction of axonemal dynein heavy chain Mdnah5 inhibitsependymal flow and reveals a novel mechanism for hydrocephalus formation. Hum Mol Genet 13, 2133–2141.
doi: 10.1093/hmg/ddh219
|
|
Iomini, C., Li, L., Esparza, J.M., and Dutcher, S.K. (2009). Retrograde intraflagellar transport mutants identify complex A proteins withmultiple genetic interactions in Chlamydomonas reinhardtii. Genetics 183, 885–896.
doi: 10.1534/genetics.109.101915
|
|
Jacoby, M., Cox, J.J., Gayral, S., Hampshire, D.J., Ayub, M., Blockmans, M., Pernot, E., Kisseleva, M.V., Compère, P., Schiffmann, S.N., et al. (2009). INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human andmouse. Nat Genet 41, 1027–1031.
doi: 10.1038/ng.427
|
|
Jarvik, J.W., and Rosenbaum, J.L. (1980). Oversized flagellar membrane protein in paralyzed mutantsof Chlamydomonas reinhardrii. J Cell Biol 85, 258–272.
doi: 10.1083/jcb.85.2.258
|
|
Jin, H., White, S.R., Shida, T., Schulz, S., Aguiar, M., Gygi, S.P., Bazan, J.F., and Nachury, M.V. (2010). The conserved Bardet-Biedl syndrome proteins assemblea coat that traffics membrane proteins to cilia. Cell 141, 1208–1219.
doi: 10.1016/j.cell.2010.05.015
|
|
Jonassen, J.A., San Agustin, J., Follit, J.A., and Pazour, G.J. (2008). Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle andcystic kidney disease. J Cell Biol 183, 377–384.
doi: 10.1083/jcb.200808137
|
|
Jones, C., Roper, V.C., Foucher, I., Qian, D., Banizs, B., Petit, C., Yoder, B.K., and Chen, P. (2008). Ciliary proteins link basal body polarization to planarcell polarity regulation. Nat Genet 40, 69–77.
doi: 10.1038/ng.2007.54
|
|
Karlstrom, R.O., Tyurina, O.V., Kawakami, A., Nishioka, N., Talbot, W.S., Sasaki, H., and Schier, A.F. (2003). Genetic analysis of zebrafish gli1 and gli2 reveals divergent requirements for gligenes in vertebrate development. Development 130, 1549–1564.
doi: 10.1242/dev.00364
|
|
Keller, L.C., Romijn, E.P., Zamora, I., Yates, J.R. 3rd, and Marshall, W.F. (2005). Proteomic analysis of isolated chlamydomonas centriolesreveals orthologs of ciliary-disease genes. Curr Biol 15, 1090–1098.
doi: 10.1016/j.cub.2005.05.024
|
|
Kim, J., Krishnaswami, S.R., and Gleeson, J.G. (2008). CEP290 interacts with the centriolar satellite component PCM-1 and is requiredfor Rab8 localization to the primary cilium. Hum Mol Genet 17, 3796–3805.
doi: 10.1093/hmg/ddn277
|
|
K?nig, G., and Hausen, P. (1993). Planar polarity in the ciliated epidermis of Xenopusembryos. Dev Biol 160, 355–368.
doi: 10.1006/dbio.1993.1312
|
|
Kozminski, K.G., Johnson, K.A., Forscher, P., and Rosenbaum, J.L. (1993). A motility in the eukaryotic flagellum unrelated to flagellar beating. Proc Natl Acad Sci U S A 90, 5519–5523.
doi: 10.1073/pnas.90.12.5519
|
|
Kramer-Zucker, A.G., Olale, F., Haycraft, C.J., Yoder, B.K., Schier, A.F., and Drummond, I.A. (2005). Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer’svesicle is required for normal organogenesis. Development 132, 1907–1921.
doi: 10.1242/dev.01772
|
|
Lechtreck, K.F., Johnson, E.C., Sakai, T., Cochran, D., Ballif, B.A., Rush, J., Pazour, G.J., Ikebe, M., and Witman, G.B. (2009). The Chlamydomonas reinhardtii BBSome is an IFT cargo required for exportof specific signaling proteins from flagella. J Cell Biol 187, 1117–1132.
doi: 10.1083/jcb.200909183
|
|
Lehman, J.M., Laag, E., Michaud, E.J., and Yoder, B.K. (2009). An essential role for dermal primary cilia in hair follicle morphogenesis. J Invest Dermatol 129, 438–448.
doi: 10.1038/jid.2008.279
|
|
Liu, A., Wang, B., and Niswander, L.A. (2005). Mouse intraflagellar transport proteins regulate both the activator andrepressor functions of Gli transcription factors. Development 132, 3103–3111.
doi: 10.1242/dev.01894
|
|
Liu, Y., Pathak, N., Kramer-Zucker, A., and Drummond, I.A. (2007). Notch signaling controls the differentiation of transporting epithelia andmulticiliated cells in the zebrafish pronephros. Development 134, 1111–1122.
doi: 10.1242/dev.02806
|
|
Louie, C.M., Caridi, G., Lopes, V.S., Brancati, F., Kispert, A., Lancaster, M.A., Schlossman, A.M., Otto, E.A., Leitges, M., Gr?ne, H.J., et al. (2010). AHI1 is required for photoreceptor outer segment development and is a modifierfor retinal degeneration in nephronophthisis. Nat Genet 42, 175–180.
doi: 10.1038/ng.519
|
|
Ma, M., and Jiang, Y.J. (2007). Jagged2a-notch signaling mediates cell fate choice inthe zebrafish pronephric duct. PLoS Genet 3, e18.
doi: 10.1371/journal.pgen.0030018
|
|
Maria, B.L., Quisling, R.G., Rosainz, L.C., Yachnis, A.T., Gitten, J., Dede, D., and Fennell, E. (1999). Molar tooth sign in Joubert syndrome: clinical, radiologic, and pathologic significance. J Child Neurol 14, 368–376.
doi: 10.1177/088307389901400605
|
|
Marnellos, G., Deblandre, G.A., Mjolsness, E., and Kintner, C. (2000). Delta-Notch lateral inhibitory patterning in the emergence of ciliated cells in Xenopus:experimental observations and a gene network model. Pac Symp Biocomput 5, 326–337.
|
|
Marshall, W.F., and Rosenbaum, J.L. (2001). Intraflagellar transport balances continuous turnoverof outer doublet microtubules: implications for flagellar length control. J Cell Biol 155, 405–414.
doi: 10.1083/jcb.200106141
|
|
May, S.R., Ashique, A.M., Karlen, M., Wang, B., Shen, Y., Zarbalis, K., Reiter, J., Ericson, J., and Peterson, A.S. (2005). Loss of the retrograde motor for IFT disrupts localization of Smo to ciliaand prevents the expression of both activator and repressor functionsof Gli. Dev Biol 287, 378–389.
doi: 10.1016/j.ydbio.2005.08.050
|
|
McDermott, K.M., Liu, B.Y., Tlsty, T.D., and Pazour, G.J. (2010). Primary cilia regulate branching morphogenesis duringmammary gland development. Curr Biol 20, 731–737.
doi: 10.1016/j.cub.2010.02.048
|
|
McVittie, A. (1972). Flagellum mutants of Chlamydomonasreinhardii. J Gen Microbiol 71, 525–540.
|
|
Meng, X., Noyes, M.B., Zhu, L.J., Lawson, N.D., and Wolfe, S.A. (2008). Targeted gene inactivation in zebrafish using engineeredzinc-finger nucleases. Nat Biotechnol 26, 695–701.
doi: 10.1038/nbt1398
|
|
Mitchell, B., Jacobs, R., Li, J., Chien, S., and Kintner, C. (2007). A positive feedback mechanism governs the polarity andmotion of motile cilia. Nature 447, 97–101.
doi: 10.1038/nature05771
|
|
Mitchell, B., Stubbs, J.L., Huisman, F., Taborek, P., Yu, C., and Kintner, C. (2009). The PCP pathwayinstructs the planar orientation of ciliated cells in the Xenopuslarval skin. Curr Biol 19, 924–929.
doi: 10.1016/j.cub.2009.04.018
|
|
Mochizuki, T., Wu, G., Hayashi, T., Xenophontos, S.L., Veldhuisen, B., Saris, J.J., Reynolds, D.M., Cai, Y., Gabow, P.A., Pierides, A., et al. (1996). PKD2, a gene for polycystic kidney diseasethat encodes an integral membrane protein. Science 272, 1339–1342.
doi: 10.1126/science.272.5266.1339
|
|
Murga-Zamalloa, C.A., Swaroop, A., and Khanna, H. (2009). RPGR-containing protein complexes in syndromic and non-syndromic retinal degenerationdue to ciliary dysfunction. J Genet 88, 399–407.
doi: 10.1007/s12041-009-0061-7
|
|
Nasevicius, A., and Ekker, S.C. (2000). Effective targeted gene ‘knockdown’ in zebrafish. Nat Genet 26, 216–220.
doi: 10.1038/79951
|
|
Nonaka, S., Tanaka, Y., Okada, Y., Takeda, S., Harada, A., Kanai, Y., Kido, M., and Hirokawa, N. (1998). Randomization of left-right asymmetry due to loss ofnodal cilia generating leftward flow of extraembryonic fluid in micelacking KIF3B motor protein. Cell 95, 829–837.
doi: 10.1016/S0092-8674(00)81705-5
|
|
Nonaka, S., Shiratori, H., Saijoh, Y., and Hamada, H. (2002). Determination of left-right patterning of the mouse embryo by artificial nodal flow. Nature 418, 96–99.
doi: 10.1038/nature00849
|
|
Ocbina, P.J., Tuson, M., Anderson, K.V., and Heisenberg, C.-P. (2009). Primary cilia are not required for normal canonical Wnt signaling in the mouseembryo. PLoS ONE 4, e6839.
doi: 10.1371/journal.pone.0006839
|
|
Otto, E.A., Schermer, B., Obara, T., O'Toole, J.F., Hiller, K.S., Mueller, A.M., Ruf, R.G., Hoefele, J., Beekmann, F., Landau, D., et al. (2003). Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic diseaseto the function of primary cilia and left-right axis determination. Nat Genet 34, 413–420.
doi: 10.1038/ng1217
|
|
Parisi, M.A., Bennett, C.L., Eckert, M.L., Dobyns, W.B., Gleeson, J.G., Shaw, D.W., McDonald, R., Eddy, A., Chance, P.F., and Glass, I.A. (2004). The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset ofindividuals with Joubert syndrome. Am J Hum Genet 75, 82–91.
doi: 10.1086/421846
|
|
Parisi, M.A., Doherty, D., Chance, P.F., and Glass, I.A. (2007). Joubert syndrome (and related disorders) (OMIM 213300). Eur J Hum Genet 15, 511–521.
doi: 10.1038/sj.ejhg.5201648
|
|
Park, T.J., Haigo, S.L., and Wallingford, J.B. (2006). Ciliogenesis defects in embryos lacking inturned or fuzzy function are associatedwith failure of planar cell polarity and Hedgehog signaling. Nat Genet 38, 303–311.
doi: 10.1038/ng1753
|
|
Park, T.J., Mitchell, B.J., Abitua, P.B., Kintner, C., and Wallingford, J.B. (2008). Dishevelled controls apical docking and planar polarizationof basal bodies in ciliated epithelial cells. Nat Genet 40, 871–879.
doi: 10.1038/ng.104
|
|
Pazour, G.J., Wilkerson, C.G., and Witman, G.B. (1998). A dynein light chain is essential for the retrograde particle movement of intraflagellartransport (IFT). J Cell Biol 141, 979–992.
doi: 10.1083/jcb.141.4.979
|
|
Pazour, G.J., Dickert, B.L., Vucica, Y., Seeley, E.S., Rosenbaum, J.L., Witman, G.B., and Cole, D.G. (2000). Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, arerequired for assembly of cilia and flagella. J Cell Biol 151, 709–718.
doi: 10.1083/jcb.151.3.709
|
|
Pazour, G.J., San Agustin, J.T., Follit, J.A., Rosenbaum, J.L., and Witman, G.B. (2002). Polycystin-2 localizes to kidney cilia and the ciliarylevel is elevated in orpk mice with polycystic kidney disease. Curr Biol 12, R378–R380.
doi: 10.1016/S0960-9822(02)00877-1
|
|
Pedersen, L.B., and Rosenbaum, J.L. (2008). Intraflagellar transport (IFT) role in ciliary assembly,resorption and signalling. Curr Top Dev Biol 85, 23–61.
doi: 10.1016/S0070-2153(08)00802-8
|
|
Perkins, L.A., Hedgecock, E.M., Thomson, J.N., and Culotti, J.G. (1986). Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev Biol 117, 456–487.
doi: 10.1016/0012-1606(86)90314-3
|
|
Piperno, G., Siuda, E., Henderson, S., Segil, M., Vaananen, H., and Sassaroli, M. (1998). Distinct mutants of retrograde intraflagellar transport (IFT) share similarmorphological and molecular defects. J Cell Biol 143, 1591–1601.
doi: 10.1083/jcb.143.6.1591
|
|
Ross, A.J., May-Simera, H., Eichers, E.R., Kai, M., Hill, J., Jagger, D.J., Leitch, C.C., Chapple, J.P., Munro, P.M., Fisher, S., et al. (2005). Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet 37, 1135–1140.
doi: 10.1038/ng1644
|
|
Qin, H., Rosenbaum, J.L., and Barr, M.M. (2001). An autosomal recessive polycystic kidney disease gene homolog is involved in intraflagellartransport in C. elegans ciliated sensory neurons. Curr Biol 11, 457–461.
doi: 10.1016/S0960-9822(01)00122-1
|
|
Reese, T.S. (1965). Olfactory cilia in the frog. J Cell Biol 25, 209–230.
doi: 10.1083/jcb.25.2.209
|
|
Rohatgi, R., Milenkovic, L., and Scott, M.P. (2007). Patched1 regulates hedgehog signaling at the primary cilium. Science 317, 372–376.
doi: 10.1126/science.1139740
|
|
Romio, L., Fry, A.M., Winyard, P.J., Malcolm, S., Woolf, A.S., and Feather, S.A. (2004). OFD1 is a centrosomal/basal body protein expressed during mesenchymal-epithelialtransition in human nephrogenesis. J Am Soc Nephrol 15, 2556–2568.
doi: 10.1097/01.ASN.0000140220.46477.5C
|
|
Rosenbaum, J.L., and Witman, G.B. (2002). Intraflagellar transport. Nat Rev Mol Cell Biol 3, 813–825.
doi: 10.1038/nrm952
|
|
Sanderson, M.J., and Sleigh, M.A. (1981). Ciliary activity of cultured rabbit tracheal epithelium:beat pattern and metachrony. J Cell Sci 47, 331–347.
|
|
Satran, D., Pierpont, M.E., and Dobyns, W.B. (1999). Cerebello-oculo-renal syndromes including Arima, Senior-L?ken and COACH syndromes:more than just variants of Joubert syndrome. Am J Med Genet 86, 459–469.
doi: 10.1002/(SICI)1096-8628(19991029)86:5<459::AID-AJMG12>3.0.CO;2-C
|
|
Sayer, J.A., Otto, E.A., O’Toole, J.F., Nurnberg, G., Kennedy, M.A., Becker, C., Hennies, H.C., Helou, J., Attanasio, M., Fausett, B.V., et al. (2006). The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcriptionfactor ATF4. Nat Genet 38, 674–681.
doi: 10.1038/ng1786
|
|
Schafer, J.C., Haycraft, C.J., Thomas, J.H., Yoder, B.K., and Swoboda, P. (2003). XBX-1 encodes a dynein light intermediate chain requiredfor retrograde intraflagellar transport and cilia assembly in Caenorhabditiselegans. Mol Biol Cell 14, 2057–2070.
doi: 10.1091/mbc.E02-10-0677
|
|
Schneider, L., Clement, C.A., Teilmann, S.C., Pazour, G.J., Hoffmann, E.K., Satir, P., and Christensen, S.T. (2005). PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Curr Biol 15, 1861–1866.
doi: 10.1016/j.cub.2005.09.012
|
|
Schrick, J.J., Onuchic, L.F., Reeders, S.T., Korenberg, J., Chen, X.N., Moyer, J.H., Wilkinson, J.E., and Woychik, R.P. (1995). Characterization of the human homologue of the mouse Tg737 candidate polycystic kidneydisease gene. Hum Mol Genet 4, 559–567.
doi: 10.1093/hmg/4.4.559
|
|
Shah, A.S., Ben-Shahar, Y., Moninger, T.O., Kline, J.N., and Welsh, M.J. (2009). Motile cilia of human airway epithelia are chemosensory. Science 325, 1131–1134.
doi: 10.1126/science.1173869
|
|
Shintani, K., Shechtman, D.L., and Gurwood, A.S. (2009). Review and update: current treatment trends for patients with retinitis pigmentosa. Optometry 80, 384–401.
doi: 10.1016/j.optm.2008.01.026
|
|
Simons, M., Gloy, J., Ganner, A., Bullerkotte, A., Bashkurov, M., Kr?nig, C., Schermer, B., Benzing, T., Cabello, O.A., Jenny, A., et al. (2005). Inversin, the gene product mutated in nephronophthisistype II, functions as a molecular switch between Wnt signaling pathways. Nat Genet, 37, 537–543.
doi: 10.1038/ng1552
|
|
Spassky, N., Han, Y.G., Aguilar, A., Strehl, L., Besse, L., Laclef, C., Ros, M.R., Garcia-Verdugo, J.M., and Alvarez-Buylla, A. (2008). Primary cilia are required for cerebellar development and Shh-dependent expansionof progenitor pool. Dev Biol 317, 246–259.
doi: 10.1016/j.ydbio.2008.02.026
|
|
Sun, Z., Amsterdam, A., Pazour, G.J., Cole, D.G., Miller, M.S., and Hopkins, N. (2004). A genetic screen in zebrafish identifies cilia genes as a principal cause ofcystic kidney. Development 131, 4085–4093.
doi: 10.1242/dev.01240
|
|
Tallila, J., Jakkula, E., Peltonen, L., Salonen, R., and Kestil?, M. (2008). Identification of CC2D2A as a Meckel syndrome gene addsan important piece to the ciliopathy puzzle. Am J Hum Genet 82, 1361–1367.
doi: 10.1016/j.ajhg.2008.05.004
|
|
Tam, L.W., Wilson, N.F., and Lefebvre, P.A. (2007). A CDK-related kinase regulates the length and assembly of flagella in Chlamydomonas. J Cell Biol 176, 819–829.
doi: 10.1083/jcb.200610022
|
|
Tammachote, R., Hommerding, C.J., Sinders, R.M., Miller, C.A., Czarnecki, P.G., Leightner, A.C., Salisbury, J.L., Ward, C.J., Torres, V.E., Gattone, V.H. 2nd, et al. (2009). Ciliary and centrosomal defects associated with mutation and depletion ofthe Meckel syndrome genes MKS1 and MKS3. Hum Mol Genet 18, 3311–3323.
doi: 10.1093/hmg/ddp272
|
|
Tran, P.V., Haycraft, C.J., Besschetnova, T.Y., Turbe-Doan, A., Stottmann, R.W., Herron, B.J., Chesebro, A.L., Qiu, H., Scherz, P.J., Shah, J.V., et al. (2008). THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellartransport in cilia. Nat Genet 40, 403–410.
doi: 10.1038/ng.105
|
|
Tsao, P.N., Vasconcelos, M., Izvolsky, K.I., Qian, J., Lu, J., and Cardoso, W.V. (2009). Notchsignaling controls the balance of ciliated and secretory cell fatesin developing airways. Development 136, 2297–2307.
doi: 10.1242/dev.034884
|
|
Tsujikawa, M., and Malicki, J. (2004). Intraflagellar transport genes are essential for differentiationand survival of vertebrate sensory neurons. Neuron 42, 703–716.
doi: 10.1016/S0896-6273(04)00268-5
|
|
Valente, E.M., Silhavy, J.L., Brancati, F., Barrano, G., Krishnaswami, S.R., Castori, M., Lancaster, M.A., Boltshauser, E., Boccone, L., Al-Gazali, L., et al, and the International Joubert Syndrome Related Disorders Study Group. (2006). Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropicforms of Joubert syndrome. Nat Genet 38, 623–625.
doi: 10.1038/ng1805
|
|
Valente, E.M., Logan, C.V., Mougou-Zerelli, S., Lee, J.H., Silhavy, J.L., Brancati, F., Iannicelli, M., Travaglini, L., Romani, S., Illi, B., et al. (2010). Mutations in TMEM216 perturb ciliogenesis andcause Joubert, Meckel and related syndromes. Nat Genet42, 619-625.
|
|
Vierkotten, J., Dildrop, R., Peters, T., Wang, B., and Rüther, U. (2007). Ftm is a novel basal body protein of cilia involvedin Shh signalling. Development 134, 2569–2577.
doi: 10.1242/dev.003715
|
|
Vladar, E.K., and Axelrod, J.D. (2008). Dishevelled links basal body docking and orientationin ciliated epithelial cells. Trends Cell Biol 18, 517–520.
doi: 10.1016/j.tcb.2008.08.004
|
|
Wallace, V.A. (1999). Purkinje-cell-derived Sonic hedgehogregulates granule neuron precursor cell proliferation in the developingmouse cerebellum. Curr Biol 9, 445–448.
doi: 10.1016/S0960-9822(99)80195-X
|
|
Wechsler-Reya, R.J., and Scott, M.P. (1999). Control of neuronal precursor proliferation in the cerebellumby Sonic Hedgehog. Neuron 22, 103–114.
doi: 10.1016/S0896-6273(00)80682-0
|
|
Wheatley, D.N. (1995). Primary cilia in normal and pathologicaltissues. Pathobiology 63, 222–238.
doi: 10.1159/000163955
|
|
White, R.M., Sessa, A., Burke, C., Bowman, T., LeBlanc, J., Ceol, C., Bourque, C., Dovey, M., Goessling, W., Burns, C.E., et al. (2008). Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell 2, 183–189.
doi: 10.1016/j.stem.2007.11.002
|
|
Wolf, M.T., Saunier, S., O’Toole, J.F., Wanner, N., Groshong, T., Attanasio, M., Salomon, R., Stallmach, T., Sayer, J.A., Waldherr, R., et al. (2007). Mutational analysis of the RPGRIP1L gene in patients with Joubert syndrome and nephronophthisis. Kidney Int 72, 1520–1526.
doi: 10.1038/sj.ki.5002630
|
|
Wright, A.F., Chakarova, C.F., Abd El-Aziz, M.M., and Bhattacharya, S.S. (2010). Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait. Nat Rev Genet 11, 273–284.
doi: 10.1038/nrg2717
|
|
Yoder, B.K., Hou, X., and Guay-Woodford, L.M. (2002a). The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris,and cystin, are co-localized in renal cilia. J Am Soc Nephrol 13, 2508–2516.
doi: 10.1097/01.ASN.0000029587.47950.25
|
|
Yoder, B.K., Tousson, A., Millican, L., Wu, J.H., Bugg, C.E. Jr, Schafer, J.A., and Balkovetz, D.F. (2002b). Polaris, a protein disrupted in orpk mutant mice, is required for assemblyof renal cilium. Am J Physiol Renal Physiol 282, F541–F552.
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
