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Pediatric Nephrology

, Volume 26, Issue 5, pp 655–662 | Cite as

The primary cilium in different tissues—lessons from patients and animal models

  • Anna D’Angelo
  • Brunella FrancoEmail author
Review

Abstract

Primary cilia are specialized organelles consisting of an axoneme anchored to the plasma membrane through the basal body consisting of two centrioles. They protrude from the cell surface of almost all mammalian cells. Mutations in genes encoding for ciliary proteins cause ciliopathies, which are characterized by a wide spectrum of phenotypes, including polycystic kidney, hepatic disease, malformations in the central nervous system, skeletal defects, retinal degeneration, and obesity. Both clinical studies and animal models have revealed that during embryogenesis, primary cilium play an essential role in defining the correct patterning of the body. In this study, we focused our attention on the tissues mainly affected in ciliopathies, such as the kidney, liver, and central nervous system. Emerging studies reveal that the primary cilium may play similar roles, leading to distinct functions according to the different cell type and developmental stages. The state of the art in primary cilia studies reveals a very complex role. The aim of this review is to evaluate the recent advances in the function of primary cilia in different tissues, underlining similarities and differences.

Keywords

Primary cilium Polycystic kidney disease Mechano-sensor Osmo-sensor Chemo-sensor Kidney Liver Neurons 

Notes

Acknowledgments

We apologize to our colleagues whose insightful work was not included due to size constraints. This work was supported by a grant from the Italian Telethon Foundation and grant EUCILIA-HEALTH-F2-2007-201804.

References

  1. 1.
    Satir P, Christensen ST (2007) Overview of structure and function of mammalian cilia. Annu Rev Physiol 69:377–400PubMedCrossRefGoogle Scholar
  2. 2.
    Satir P, Pedersen LB, Christensen ST (2010) The primary cilium at a glance. J Cell Sci 123:499–503PubMedCrossRefGoogle Scholar
  3. 3.
    Seeley ES, Nachury MV (2010) The perennial organelle: assembly and disassembly of the primary cilium. J Cell Sci 123:511–518PubMedCrossRefGoogle Scholar
  4. 4.
    Molla-Herman A, Ghossoub R, Blisnick T, Meunier A, Serres C, Silbermann F, Emmerson C, Romeo K, Bourdoncle P, Schmitt A, Saunier S, Spassky N, Bastin P, Benmerah A (2010) The ciliary pocket: an endocytic membrane domain at the base of primary and motile cilia. J Cell Sci 123:1785–1795PubMedCrossRefGoogle Scholar
  5. 5.
    Nonaka S, Tanaka Y, Okada Y, Takeda S, Harada A, Kanai Y, Kido M, Hirokawa N (1998) Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95:829–837PubMedCrossRefGoogle Scholar
  6. 6.
    Hirokawa N, Tanaka Y, Okada Y (2009) Left-right determination: involvement of molecular motor KIF3, cilia, and nodal flow. Cold Spring Harb Perspect Biol 1:a000802PubMedCrossRefGoogle Scholar
  7. 7.
    Basu B, Brueckner M (2008) Cilia multifunctional organelles at the center of vertebrate left-right asymmetry. Curr Top Dev Biol 85:151–174PubMedCrossRefGoogle Scholar
  8. 8.
    Quarmby LM, Parker JD (2005) Cilia and the cell cycle? J Cell Biol 169:707–710PubMedCrossRefGoogle Scholar
  9. 9.
    Kim J, Lee JE, Heynen-Genel S, Suyama E, Ono K, Lee K, Ideker T, Aza-Blanc P, Gleeson JG (2010) Functional genomic screen for modulators of ciliogenesis and cilium length. Nature 464:1048–1051PubMedCrossRefGoogle Scholar
  10. 10.
    Kozminski KG, Johnson KA, Forscher P, Rosenbaum JL (1993) A motility in the eukaryotic flagellum unrelated to flagellar beating. Proc Natl Acad Sci USA 90:5519–5523PubMedCrossRefGoogle Scholar
  11. 11.
    Cole DG, Chinn SW, Wedaman KP, Hall K, Vuong T, Scholey JM (1993) Novel heterotrimeric kinesin-related protein purified from sea urchin eggs. Nature 366:268–270PubMedCrossRefGoogle Scholar
  12. 12.
    Pazour GJ, Wilkerson CG, Witman GB (1998) A dynein light chain is essential for the retrograde particle movement of intraflagellar transport (IFT). J Cell Biol 141:979–992PubMedCrossRefGoogle Scholar
  13. 13.
    Signor D, Wedaman KP, Orozco JT, Dwyer ND, Bargmann CI, Rose LS, Scholey JM (1999) Role of a class DHC1b dynein in retrograde transport of IFT motors and IFT raft particles along cilia, but not dendrites, in chemosensory neurons of living Caenorhabditis elegans. J Cell Biol 147:519–530PubMedCrossRefGoogle Scholar
  14. 14.
    Inglis PN, Boroevich KA, Leroux MR (2006) Piecing together a ciliome. Trends Genet 22:491–500PubMedCrossRefGoogle Scholar
  15. 15.
    Gherman A, Davis EE, Katsanis N (2006) The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia. Nat Genet 38:961–962PubMedCrossRefGoogle Scholar
  16. 16.
    Ostrowski LE, Blackburn K, Radde KM, Moyer MB, Schlatzer DM, Moseley A, Boucher RC (2002) A proteomic analysis of human cilia: identification of novel components. Mol Cell Proteomics 1:451–465PubMedCrossRefGoogle Scholar
  17. 17.
    Lancaster MA, Gleeson JG (2009) The primary cilium as a cellular signaling center: lessons from disease. Curr Opin Genet Dev 19:220–229PubMedCrossRefGoogle Scholar
  18. 18.
    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
  19. 19.
    D'Angelo A, Franco B (2009) The dynamic cilium in human diseases. Pathogenetics 2:3PubMedCrossRefGoogle Scholar
  20. 20.
    Wilson PD (2004) Polycystic kidney disease: new understanding in the pathogenesis. Int J Biochem Cell Biol 36:1868–1873PubMedCrossRefGoogle Scholar
  21. 21.
    Deltas C, Papagregoriou G (2010) Cystic diseases of the kidney: molecular biology and genetics. Arch Pathol Lab Med 134:569–582PubMedGoogle Scholar
  22. 22.
    Yoder BK (2007) Role of primary cilia in the pathogenesis of polycystic kidney disease. J Am Soc Nephrol 18:1381–1388PubMedCrossRefGoogle Scholar
  23. 23.
    Wilson PD (2008) Mouse models of polycystic kidney disease. Curr Top Dev Biol 84:311–350PubMedCrossRefGoogle Scholar
  24. 24.
    Ferrante MI, Zullo A, Barra A, Bimonte S, Messaddeq N, Studer M, Dolle P, Franco B (2006) Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat Genet 38:112–117PubMedCrossRefGoogle Scholar
  25. 25.
    Zullo A, Iaconis D, Barra A, Cantone A, Messaddeq N, Capasso G, Dolle P, Igarashi P, Franco B (2010) Kidney-specific inactivation of Ofd1 leads to renal cystic disease associated with upregulation of the mTOR pathway. Hum Mol Genet 19:2792–2803PubMedCrossRefGoogle Scholar
  26. 26.
    Jonassen JA, San Agustin J, Follit JA, Pazour GJ (2008) Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease. J Cell Biol 183:377–384PubMedCrossRefGoogle Scholar
  27. 27.
    Bonnet CS, Aldred M, von Ruhland C, Harris R, Sandford R, Cheadle JP (2009) Defects in cell polarity underlie TSC and ADPKD-associated cystogenesis. Hum Mol Genet 18:2166–2176PubMedCrossRefGoogle Scholar
  28. 28.
    Fischer E, Legue E, Doyen A, Nato F, Nicolas JF, Torres V, Yaniv M, Pontoglio M (2006) Defective planar cell polarity in polycystic kidney disease. Nat Genet 38:21–23PubMedCrossRefGoogle Scholar
  29. 29.
    Praetorius HA, Spring KR (2005) A physiological view of the primary cilium. Annu Rev Physiol 67:515–529PubMedCrossRefGoogle Scholar
  30. 30.
    Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33:129–137PubMedCrossRefGoogle Scholar
  31. 31.
    Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hiesberger T, Igarashi P, Bennett AM, Ibraghimov-Beskrovnaya O, Somlo S, Caplan MJ (2004) Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J Clin Invest 114:1433–1443PubMedGoogle Scholar
  32. 32.
    Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Kronig C, Schermer B, Benzing T, Cabello OA, Jenny A, Mlodzik M, Polok B, Driever W, Obara T, Walz G (2005) Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet 37:537–543PubMedCrossRefGoogle Scholar
  33. 33.
    Bergmann C, Fliegauf M, Bruchle NO, Frank V, Olbrich H, Kirschner J, Schermer B, Schmedding I, Kispert A, Kranzlin B, Nurnberg G, Becker C, Grimm T, Girschick G, Lynch SA, Kelehan P, Senderek J, Neuhaus TJ, Stallmach T, Zentgraf H, Nurnberg P, Gretz N, Lo C, Lienkamp S, Schafer T, Walz G, Benzing T, Zerres K, Omran H (2008) Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia. Am J Hum Genet 82:959–970PubMedCrossRefGoogle Scholar
  34. 34.
    Piontek K, Menezes LF, Garcia-Gonzalez MA, Huso DL, Germino GG (2007) A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med 13:1490–1495PubMedCrossRefGoogle Scholar
  35. 35.
    Lantinga-van Leeuwen IS, Leonhard WN, van der Wal A, Breuning MH, de Heer E, Peters DJ (2007) Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet 16:3188–3196PubMedCrossRefGoogle Scholar
  36. 36.
    Huang BQ, Masyuk TV, Muff MA, Tietz PS, Masyuk AI, Larusso NF (2006) Isolation and characterization of cholangiocyte primary cilia. Am J Physiol Gastrointest Liver Physiol 291:G500–G509PubMedCrossRefGoogle Scholar
  37. 37.
    Masyuk AI, Masyuk TV, LaRusso NF (2008) Cholangiocyte primary cilia in liver health and disease. Dev Dyn 237:2007–2012PubMedCrossRefGoogle Scholar
  38. 38.
    Onori P, Franchitto A, Mancinelli R, Carpino G, Alvaro D, Francis H, Alpini G, Gaudio E (2010) Polycystic liver diseases. Dig Liver Dis 42:261–271PubMedCrossRefGoogle Scholar
  39. 39.
    Gunay-Aygun M (2009) Liver and kidney disease in ciliopathies. Am J Med Genet C Semin Med Genet 151C:296–306PubMedCrossRefGoogle Scholar
  40. 40.
    Masyuk TV, Huang BQ, Ward CJ, Masyuk AI, Yuan D, Splinter PL, Punyashthiti R, Ritman EL, Torres VE, Harris PC, LaRusso NF (2003) Defects in cholangiocyte fibrocystin expression and ciliary structure in the PCK rat. Gastroenterology 125:1303–1310PubMedCrossRefGoogle Scholar
  41. 41.
    Clotman F, Libbrecht L, Killingsworth MC, Loo CC, Roskams T, Lemaigre FP (2008) Lack of cilia and differentiation defects in the liver of human foetuses with the Meckel syndrome. Liver Int 28:377–384PubMedCrossRefGoogle Scholar
  42. 42.
    Masyuk TV, Masyuk AI, Torres VE, Harris PC, Larusso NF (2007) Octreotide inhibits hepatic cystogenesis in a rodent model of polycystic liver disease by reducing cholangiocyte adenosine 3', 5'-cyclic monophosphate. Gastroenterology 132:1104–1116PubMedCrossRefGoogle Scholar
  43. 43.
    Stroope A, Radtke B, Huang B, Masyuk T, Torres V, Ritman E, LaRusso N (2010) Hepato-renal pathology in pkd2ws25/- mice, an animal model of autosomal dominant polycystic kidney disease. Am J Pathol 176:1282–1291PubMedCrossRefGoogle Scholar
  44. 44.
    Banales JM, Masyuk TV, Bogert PS, Huang BQ, Gradilone SA, Lee SO, Stroope AJ, Masyuk AI, Medina JF, LaRusso NF (2008) Hepatic cystogenesis is associated with abnormal expression and location of ion transporters and water channels in an animal model of autosomal recessive polycystic kidney disease. Am J Pathol 173:1637–1646PubMedCrossRefGoogle Scholar
  45. 45.
    Banales JM, Masyuk TV, Gradilone SA, Masyuk AI, Medina JF, LaRusso NF (2009) The cAMP effectors Epac and protein kinase a (PKA) are involved in the hepatic cystogenesis of an animal model of autosomal recessive polycystic kidney disease (ARPKD). Hepatology 49:160–174PubMedCrossRefGoogle Scholar
  46. 46.
    Masyuk AI, Masyuk TV, Splinter PL, Huang BQ, Stroope AJ, LaRusso NF (2006) Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling. Gastroenterology 131:911–920PubMedCrossRefGoogle Scholar
  47. 47.
    Torrice A, Cardinale V, Gatto M, Semeraro R, Napoli C, Onori P, Alpini G, Gaudio E, Alvaro D (2010) Polycystins play a key role in the modulation of cholangiocyte proliferation. Dig Liver Dis 42:377–385PubMedCrossRefGoogle Scholar
  48. 48.
    Masyuk AI, Gradilone SA, Banales JM, Huang BQ, Masyuk TV, Lee SO, Splinter PL, Stroope AJ, Larusso NF (2008) Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors. Am J Physiol Gastrointest Liver Physiol 295:G725–G734PubMedCrossRefGoogle Scholar
  49. 49.
    Gradilone SA, Masyuk AI, Splinter PL, Banales JM, Huang BQ, Tietz PS, Masyuk TV, Larusso NF (2007) Cholangiocyte cilia express TRPV4 and detect changes in luminal tonicity inducing bicarbonate secretion. Proc Natl Acad Sci USA 104:19138–19143PubMedCrossRefGoogle Scholar
  50. 50.
    Berbari NF, O'Connor AK, Haycraft CJ, Yoder BK (2009) The primary cilium as a complex signaling center. Curr Biol 19:R526–R535PubMedCrossRefGoogle Scholar
  51. 51.
    Fuchs JL, Schwark HD (2004) Neuronal primary cilia: a review. Cell Biol Int 28:111–118PubMedCrossRefGoogle Scholar
  52. 52.
    Bishop GA, Berbari NF, Lewis J, Mykytyn K (2007) Type III adenylyl cyclase localizes to primary cilia throughout the adult mouse brain. J Comp Neurol 505:562–571PubMedCrossRefGoogle Scholar
  53. 53.
    Ahdab-Barmada M, Claassen D (1990) A distinctive triad of malformations of the central nervous system in the Meckel-Gruber syndrome. J Neuropathol Exp Neurol 49:610–620PubMedCrossRefGoogle Scholar
  54. 54.
    Gitten J, Dede D, Fennell E, Quisling R, Maria BL (1998) Neurobehavioral development in Joubert syndrome. J Child Neurol 13:391–397PubMedCrossRefGoogle Scholar
  55. 55.
    Rooryck C, Pelras S, Chateil JF, Cances C, Arveiler B, Verloes A, Lacombe D, Goizet C (2007) Bardet-biedl syndrome and brain abnormalities. Neuropediatrics 38:5–9PubMedCrossRefGoogle Scholar
  56. 56.
    Lee JH, Gleeson JG (2010) The role of primary cilia in neuronal function. Neurobiol Dis 38:167–172PubMedCrossRefGoogle Scholar
  57. 57.
    Macca M, Franco B (2009) The molecular basis of oral-facial-digital syndrome, type 1. Am J Med Genet C Semin Med Genet 151C:318–325PubMedCrossRefGoogle Scholar
  58. 58.
    Chizhikov VV, Davenport J, Zhang Q, Shih EK, Cabello OA, Fuchs JL, Yoder BK, Millen KJ (2007) Cilia proteins control cerebellar morphogenesis by promoting expansion of the granule progenitor pool. J Neurosci 27:9780–9789PubMedCrossRefGoogle Scholar
  59. 59.
    Spassky N, Han YG, Aguilar A, Strehl L, Besse L, Laclef C, Ros MR, Garcia-Verdugo JM, Alvarez-Buylla A (2008) Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool. Dev Biol 317:246–259PubMedCrossRefGoogle Scholar
  60. 60.
    Han YG, Spassky N, Romaguera-Ros M, Garcia-Verdugo JM, Aguilar A, Schneider-Maunoury S, Alvarez-Buylla A (2008) Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci 11:277–284PubMedCrossRefGoogle Scholar
  61. 61.
    Breunig JJ, Sarkisian MR, Arellano JI, Morozov YM, Ayoub AE, Sojitra S, Wang B, Flavell RA, Rakic P, Town T (2008) Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling. Proc Natl Acad Sci USA 105:13127–13132PubMedCrossRefGoogle Scholar
  62. 62.
    Caspary T, Larkins CE, Anderson KV (2007) The graded response to Sonic Hedgehog depends on cilia architecture. Dev Cell 12:767–778PubMedCrossRefGoogle Scholar
  63. 63.
    Willaredt MA, Hasenpusch-Theil K, Gardner HA, Kitanovic I, Hirschfeld-Warneken VC, Gojak CP, Gorgas K, Bradford CL, Spatz J, Wolfl S, Theil T, Tucker KL (2008) A crucial role for primary cilia in cortical morphogenesis. J Neurosci 28:12887–12900PubMedCrossRefGoogle Scholar
  64. 64.
    Gorivodsky M, Mukhopadhyay M, Wilsch-Braeuninger M, Phillips M, Teufel A, Kim C, Malik N, Huttner W, Westphal H (2009) Intraflagellar transport protein 172 is essential for primary cilia formation and plays a vital role in patterning the mammalian brain. Dev Biol 325:24–32PubMedCrossRefGoogle Scholar
  65. 65.
    Stottmann RW, Tran PV, Turbe-Doan A, Beier DR (2009) Ttc21b is required to restrict sonic hedgehog activity in the developing mouse forebrain. Dev Biol 335:166–178PubMedCrossRefGoogle Scholar
  66. 66.
    Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF (2005) Vertebrate Smoothened functions at the primary cilium. Nature 437:1018–1021PubMedCrossRefGoogle Scholar
  67. 67.
    May SR, Ashique AM, Karlen M, Wang B, Shen Y, Zarbalis K, Reiter J, Ericson J, Peterson AS (2005) Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli. Dev Biol 287:378–389PubMedCrossRefGoogle Scholar
  68. 68.
    Kovacs JJ, Whalen EJ, Liu R, Xiao K, Kim J, Chen M, Wang J, Chen W, Lefkowitz RJ (2008) Beta-arrestin-mediated localization of smoothened to the primary cilium. Science 320:1777–1781PubMedCrossRefGoogle Scholar
  69. 69.
    Han YG, Alvarez-Buylla A (2010) Role of primary cilia in brain development and cancer. Curr Opin Neurobiol 20:58–67PubMedCrossRefGoogle Scholar
  70. 70.
    Whitfield JF, Chakravarthy BR (2009) The neuronal primary cilium: driver of neurogenesis and memory formation in the hippocampal dentate gyrus? Cell Signal 21:1351–1355PubMedCrossRefGoogle Scholar
  71. 71.
    Davenport JR, Watts AJ, Roper VC, Croyle MJ, van Groen T, Wyss JM, Nagy TR, Kesterson RA, Yoder BK (2007) Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Curr Biol 17:1586–1594PubMedCrossRefGoogle Scholar
  72. 72.
    Seo S, Guo DF, Bugge K, Morgan DA, Rahmouni K, Sheffield VC (2009) Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling. Hum Mol Genet 18:1323–1331PubMedCrossRefGoogle Scholar
  73. 73.
    Wong SY, Seol AD, So PL, Ermilov AN, Bichakjian CK, Epstein EH Jr, Dlugosz AA, Reiter JF (2009) Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat Med 15:1055–1061PubMedCrossRefGoogle Scholar
  74. 74.
    Lehman JM, Laag E, Michaud EJ, Yoder BK (2009) An essential role for dermal primary cilia in hair follicle morphogenesis. J Invest Dermatol 129:438–448PubMedCrossRefGoogle Scholar
  75. 75.
    Haycraft CJ, Serra R (2008) Cilia involvement in patterning and maintenance of the skeleton. Curr Top Dev Biol 85:303–332PubMedCrossRefGoogle Scholar
  76. 76.
    Temiyasathit S, Jacobs CR (2010) Osteocyte primary cilium and its role in bone mechanotransduction. Ann NY Acad Sci 1192:422–428PubMedCrossRefGoogle Scholar
  77. 77.
    Kwon RY, Temiyasathit S, Tummala P, Quah CC, Jacobs CR (2010) Primary cilium-dependent mechanosensing is mediated by adenylyl cyclase 6 and cyclic AMP in bone cells. FASEB J 24:2859–2868PubMedCrossRefGoogle Scholar
  78. 78.
    Walczak-Sztulpa J, Eggenschwiler J, Osborn D, Brown DA, Emma F, Klingenberg C, Hennekam RC, Torre G, Garshasbi M, Tzschach A, Szczepanska M, Krawczynski M, Zachwieja J, Zwolinska D, Beales PL, Ropers HH, Latos-Bielenska A, Kuss AW (2010) Cranioectodermal Dysplasia, Sensenbrenner Syndrome, Is a Ciliopathy Caused by Mutations in the IFT122 Gene. Am J Hum Genet 86:949–956PubMedCrossRefGoogle Scholar
  79. 79.
    Thivichon-Prince B, Couble ML, Giamarchi A, Delmas P, Franco B, Romio L, Struys T, Lambrichts I, Ressnikoff D, Magloire H, Bleicher F (2009) Primary cilia of odontoblasts: possible role in molar morphogenesis. J Dent Res 88:910–915PubMedCrossRefGoogle Scholar
  80. 80.
    McDermott KM, Liu BY, Tlsty TD, Pazour GJ (2010) Primary cilia regulate branching morphogenesis during mammary gland development. Curr Biol. doi: 10.1016/j.cub.2010.02.048 Google Scholar
  81. 81.
    Cervantes S, Lau J, Cano DA, Borromeo-Austin C, Hebrok M (2010) Primary cilia regulate Gli/Hedgehog activation in pancreas. Proc Natl Acad Sci USA 107:10109–10114PubMedCrossRefGoogle Scholar
  82. 82.
    Nielsen SK, Mollgard K, Clement CA, Veland IR, Awan A, Yoder BK, Novak I, Christensen ST (2008) Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines. Dev Dyn 237:2039–2052PubMedCrossRefGoogle Scholar
  83. 83.
    Ramamurthy V, Cayouette M (2009) Development and disease of the photoreceptor cilium. Clin Genet 76:137–145PubMedCrossRefGoogle Scholar
  84. 84.
    Adams NA, Awadein A, Toma HS (2007) The retinal ciliopathies. Ophthalmic Genet 28:113–125PubMedCrossRefGoogle Scholar
  85. 85.
    Clement CA, Kristensen SG, Mollgard K, Pazour GJ, Yoder BK, Larsen LA, Christensen ST (2009) The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation. J Cell Sci 122:3070–3082PubMedCrossRefGoogle Scholar
  86. 86.
    Slough J, Cooney L, Brueckner M (2008) Monocilia in the embryonic mouse heart suggest a direct role for cilia in cardiac morphogenesis. Dev Dyn 237:2304–2314PubMedCrossRefGoogle Scholar
  87. 87.
    Poelmann RE, Van der Heiden K, Gittenberger-de Groot A, Hierck BP (2008) Deciphering the endothelial shear stress sensor. Circulation 117:1124–1126PubMedCrossRefGoogle Scholar
  88. 88.
    Van der Heiden K, Hierck BP, Krams R, de Crom R, Cheng C, Baiker M, Pourquie MJ, Alkemade FE, DeRuiter MC, Gittenberger-de Groot AC, Poelmann RE (2008) Endothelial primary cilia in areas of disturbed flow are at the base of atherosclerosis. Atherosclerosis 196:542–550PubMedCrossRefGoogle Scholar
  89. 89.
    Hierck BP, Van der Heiden K, Alkemade FE, Van de Pas S, Van Thienen JV, Groenendijk BC, Bax WH, Van der Laarse A, Deruiter MC, Horrevoets AJ, Poelmann RE (2008) Primary cilia sensitize endothelial cells for fluid shear stress. Dev Dyn 237:725–735PubMedCrossRefGoogle Scholar

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© IPNA 2010

Authors and Affiliations

  1. 1.Telethon Institute of Genetics and Medicine (TIGEM)NaplesItaly
  2. 2.Medical Genetics, Department of PediatricsFederico II UniversityNaplesItaly

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