Cilia and ciliopathy



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Abstract

Cilia (cilia) are organelles that are characteristic exclusively for eukaryotes and are found in protozoa, on somatic and germ cells of multicellular, as well as gametes of many plants. In humans, two main types of cilia are distinguished: motile and sensory; also in embryogenesis, it is customary to isolate special nodular cilia necessary for the normal course of gastrulation and possibly subsequent histo- and organogenesis. Motile cilia provide the movement of the liquid medium relative to the cell in the respiratory tract, the ventricular system of the brain and the fallopian tubes, or the movement of the cell itself in the case of sperm. The main function of sensory cilia is the perception of changes in the external environment and the signal molecules inside it and their conversion into intracellular signals that regulate proliferation, differentiation, and programmed cell death. Ciliopathies, a group of pathological conditions associated with impaired development, structure, and functioning of cilia, are of clinical interest. The most studied ciliopathies include polycystic kidney disease, nephronophysis, Barde-Beadle, Joubert, Mekel, Kartagener, Karoli etc. Clinical nephronophthisis and morphological analysis of the case of Caroli, syndrome is given.

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About the authors

F. A Indeykin

Kazan State Medical University

Email: f.indeickin@yandex.ru
Kazan, Russia

M. O Mavlikeev

Kazan (Volga region) Federal University

Kazan, Russia

R. V Deev

I.I. Mechnikov North-West State Medical University; Human Stem Cell Institute

Saint Petersburg, Russia; Moscow, Russia

References

  1. Satir P., Mitchell D.R., Jékely G. How did the cilium evolve? // Current topics in developmental biology. Curr. Top. Dev. Biol. 2008; 195(3): 526-40.
  2. Gao F., Warren A., Zhang Q. et al. The all-data-based evolutionary hypothesis of ciliated protists with a revised classification of the phylum Ciliophora (Eukaryota, Alveolata). Scientific Reports 2016; 6: 1-16.
  3. Leeuwenhoek A.V. Observations, communicated to the publisher by Mr. Antony van Leewenhoeck, in a dutch letter of the 9th Octob. 1676. here English'd: concerning little animals by him observed in rain-well-sea-and snow water; as also in water wherein pepper had lain infused. Philosophical Transactions of the Royal Society of London 1676; 12(133): 821-31.
  4. Bloodgood R.A. From central to rudimentary to primary: the history of an underappreciated organelle whose time has come. The primary cilium. Methods Cell Biol. 2009; 94: 3-52.
  5. Müller O.F., Fabricius O. Animalcula infusoria fluviatilia et marina. Hauniae: Typis Nicolai Mölleri. 1786.
  6. Dujardin F. Histoire naturelle des zoophytes. Infusoires, comprenant la physiologie et la classification de ces animaux et la manière de les étudier à l'aide du microscope. Roret. 1841.
  7. Khan S., Scholey J.M. Assembly, functions and evolution of archaella, flagella and cilia. Curr. Biol. 2018; 28(6): R278-92.
  8. Moran J., McKean P.G., Ginger M.L. Eukaryotic flagella: variations in form, function, and composition during evolution. BioScience 2014; 64(12): 1103-14.
  9. Venkatesh D. Primary cilia. J. Oral. Maxillofac. Pathol. 2017; 21(1): 8-10.
  10. Spasic M., Jacobs C.R. Primary cilia: cell and molecular mechanosen-sors directing whole tissue function. Semin. Cell Dev. Biol. 2017; 71: 42-52.
  11. Satir P., Christensen S.T. Overview structure and function of mammalian cilia. Annu. Rev. Physiol. 2007; 69: 377-400.
  12. Hildebrandt F., Benzing T., Katsanis N. Ciliopathies. N. Engl. J. Med. 2011; 364(16): 1533-43.
  13. McIntyre J.C., Williams C.L., Martens J.R. Smelling the roses and seeing the light: gene therapy for ciliopathies. Trends Biotechnol. 2013; 31(6): 355-63.
  14. Satir P., Guerra C., Bell A.J. Evolution and persistence of the cilium. Cell Motil. Cytoskeleton 2007; 64(12): 906-13.
  15. Cavalier-Smith T. The evolutionary origin and phylogeny of microtubules, mitotic spindles and eukaryote flagella. BioSystems 1978; 10(1-2): 93-114.
  16. Avidor-Reiss T., Maer A.M., Koundakjian E. et al. Decoding cilia function: defining specialized genes required for compartmentalized cilia biogenesis. Cell 2004; 117(4): 527-39.
  17. Mitchell D.R. The evolution of eukaryotic cilia and flagella as motile and sensory organelles. Adv. Exp. Med. Biol. 2007; 607: 130-40.
  18. O’Malley M.A., Leger M.M., Wideman J.G. et al. Concepts of the last eukaryotic common ancestor. Nat. Ecol. Evol. 2019; 3(3): 338-44.
  19. Kamiya R., Yagi T. Functional diversity of axonemal dyneins as assessed by in vitro and in vivo motility assays of Chlamydomonas mutants. Zoolog. Sci. 2014; 31(10): 633-44.
  20. Bornens M. Cell polarity: Having and making sense of direction- On the evolutionary significance of the primary cilium/centrosome organ in Metazoa. Open biology 2018; 8(8): 1-26.
  21. Gaillard D.A., Lallement A.V., Petit A.F. et al. In vivo ciliogenesis in human fetal tracheal epithelium. Am. J. Anat. 1989; 185(4): 415-28.
  22. Hagiwara H., Ohwada N., Takata K. Cell biology of normal and abnormal ciliogenesis in the ciliated epithelium. Int. Rev. Cytol. 2004; 234: 101-41.
  23. Anderson R.G.W., Brenner R.M. The formation of basal bodies (centrioles) in the Rhesus monkey oviduct. J. Cell Biol. 1971; 50(1): 10-34.
  24. Spassky N., Meunier A. The development and functions of multiciliated epithelia. Nat. Rev. Mol. Cell Biol. 2017; 18(7): 423-36.
  25. Revinski D.R., Zaragosu L-M., Boutin C. et al. CDC20B is required for deuterosome-mediated centriole production in multiciliated cells. Nat. Commun. 2018; 9(1): 1-15.
  26. Shahid U., Singh P. Emerging Picture of Deuterosome-Dependent Centriole Amplification in MCCs. Cells 2018; 7(10): 152.
  27. Zhao H., Zhu L., Zhu Y. et al. The Cep63 paralogue Deup1 enables massive de novo centriole biogenesis for vertebrate multiciliogenesis. Nat. Cell Biol. 2013; 15(12): 1434-44.
  28. Sorokin S.P. Reconstructions of centriole formation and ciliogenesis in mammalian lungs. J. Cell Sci. 1968; 3(2): 207-30.
  29. Boisvieux-Ulrich E., Lainé M.C., Sandoz D. Cytochalasin D inhibits basal body migration and ciliary elongation in quail oviduct epithelium. Cell Tissue. Res. 1990; 259(3): 443-54.
  30. Boisvieux-Ulrich E., Laine M.C., Sandoz D. In vitro effects of benzodiazepines on ciliogenesis in the quail oviduct. Cell Motil. Cytoskeleton 1987; 8(4): 333-44.
  31. Boisvieux-Ulrich E., Lainé M.C., Sandoz D. In vitro effects of colchicine and nocodazole on ciliogenesis in quail oviduct. Biol. Cell 1989; 67(1): 67-79.
  32. Yang T.T., Chong W.M., Wang W.J. et al. Super-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components. Nat. Commun. 2018; 9(1): 1-11.
  33. Delgehyr N., Sillibourne J., Bornens M. Microtubule nucleation and anchoring at the centrosome are independent processes linked by ninein function. J. Cell Sci. 2005; 118(8): 1565-75.
  34. Hinchcliffe E.H., Linck R.W. Two proteins isolated from sea urchin sperm flagella: structural components common to the stable microtubules of axonemes and centrioles. J. Cell Sci. 1998; 111(5): 585-95.
  35. Ringo D.L. Flagellar motion and fine structure of the flagellar apparatus in Chlamydomonas. J. Cell Biol. 1967; 33(3): 543-71.
  36. Marshall W.F. Basal bodies: platforms for building cilia. Curr. Top. Dev. Biol. 2008; 85: 1-22.
  37. Carvalho-Santos Z., Azimzadeh J., Pereira-Leal J.B. et al. Tracing the origins of centrioles, cilia, and flagella. J. Cell Biol. 2011; 194(2): 165-75.
  38. Nakazawa Y., Hiraki M., Kamiya R. et al. SAS-6 is a cartwheel protein that establishes the 9-fold symmetry of the centriole. Curr. Biol. 2007; 17(24): 2169-74.
  39. Keller L.C., Romijn E.P., Zamora I. et al. Proteomic analysis of isolated chlamydomonas centrioles reveals orthologs of ciliary-disease genes. Curr. Biol. 2005; 15(12): 1090-8.
  40. Vertii A., Hung H.F., Hehnly H. et al. Human basal body basics. Cilia 2016; 5: 13.
  41. Nguyen Q., Zhen L., Nanjundappa R. et al. Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells. bioRxiv. in press 2018.
  42. Tateishi K., Yamazaki Y., Nishida T. et al. Two appendages homologous between basal bodies and centrioles are formed using distinct Odf2 domains. J. Cell Biol. 2013; 203(3): 417-25.
  43. Garcia G., Reiter J.F. A primer on the mouse basal body. Cilia. 2016; 5: 17.
  44. Uzbekov R., Alieva I. Who are you, subdistal appendages of centriole? Open Biol. 2018; 8(7): 1-8.
  45. Kunimoto K., Yamazaki Y., Nishida T. et al. Coordinated ciliary beating requires Odf2-mediated polarization of basal bodies via basal feet. Cell 2012; 148(1-2): 189-200.
  46. Yang J., Gao J., Adamian M. et al. The ciliary rootlet maintains longterm stability of sensory cilia. Mol. Cell Biol. 2005; 25(10): 4129-37.
  47. Sorokin S. Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells. J. Cell Biol. 1962; 15(2): 363-77.
  48. Breslow D.K., Holland A.J. Mechanism and regulation of centriole and cilium biogenesis. Annu. Rev. Biochem. 2019; 88: 691-724.
  49. Schmidt T.I., Kleylein-Sohn J., Westendorf J. et al. Control of centriole length by CPAP and CP110. Curr. Biol. 2009; 19(12): 1005-11.
  50. Spektor A., Tsang W.Y., Khoo D. et al. Cep97 and CP110 suppress a cilia assembly program. Cell 2007; 130(4): 678-90.
  51. Molla-Herman A., Ghossoub R., Blisnick T. et al. The ciliary pocket: an endocytic membrane domain at the base of primary and motile cilia. J. Cell Sci. 2010; 123(Pt10): 1785-95.
  52. Ishikawa T. Axoneme structure from motile cilia. Cold Spring Harb. Perspect. Biol. 2017; 9(1): 1-16.
  53. Pigino G., Bui K.H., Maheshwari A. et al. Cryoelectron tomography of radial spokes in cilia and flagella. J. Cell Biol. 2011; 195(4): 673-87.
  54. King S.M. Axonemal dynein arms. Cold Spring Harbor Perspectives in Biology 2016; 8(11): 1-12.
  55. Heuser T., Raytchev M. Krell J. et al. The dynein regulatory complex is the nexin link and a major regulatory node in cilia and flagella. J. Cell Biol. 2009; 187(6): 921-33.
  56. Yang P., Yang C., Sale W.S. Flagellar radial spoke protein 2 is a calmodulin binding protein required for motility in Chlamydomonas reinhardtii. Eukaryot. Cell 2004; 3(1): 72-81.
  57. Kagami O., Kamiya R. Translocation and rotation of microtubules caused by multiple species of Chlamydomonas inner-arm dynein. J. Cell Sci. 1992; 103(3): 653-64.
  58. Teves M.E., Nagarkatti-Gude D.R., Zhang Z. et al. Mammalian axoneme central pair complex proteins: Broader roles revealed by gene knockout phenotypes. Cytoskeleton (Hoboken) 2016; 73(1): 3-22.
  59. Rosenbaum J.L., Child F.M. Flagellar regeneration in protozoan flagellates. J. Cell Biol. 1967; 34(1): 345-64.
  60. Mirvis M., Stearns T., Nelson W.J. Cilium structure, assembly, and disassembly regulated by the cytoskeleton. Biochem J. 2018; 475(14): 2329-53.
  61. Cole D.G., Chinn S.W., Wedaman K.P. et al. Novel heterotrimeric kinesin-related protein purifi ed from sea urchin eggs. Nature 1993; 366(6452): 268-70.
  62. Kozminski K.G., Beech P.L., Rosenbaum J.L. The Chlamydomonas kinesin-like protein FLA10 is involved in motility associated with the flagellar membrane. J. Cell Biol. 1995; 131: 1517-27.
  63. Scholey J.M. Intraflagellar transport motors in cilia: moving along the cell's antenna. J. Cell Biol. 2008; 180(1): 23-9.
  64. Stepanek L., Pigino G. Microtubule doublets are double-track railways for intraflagellar transport trains. Science 2016; 352(6286): 721-4.
  65. Chien A., Shih S.M., Bower R. et al. Dynamics of the IFT machinery at the ciliary tip. Elife 2017; 6: 1-25.
  66. Brown J.M., Marsala C., Kosoy R. et al. Kinesin-II is preferentially targeted to assembling cilia and is required for ciliogenesis and normal cytokinesis in Tetrahymena. Mol. Biol. Cell 1999; 10(10): 3081-96.
  67. Follit J.A., Tuft R.A., Fogarty K.E. et al. The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly. Mol. Biol. Cell 2006; 17(9): 3781-92.
  68. Blacque O.E., Reardon M.J., Li C. et al. Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes Dev. 2004; 18(13): 1630-42.
  69. Huang K., Diener D.R., Mitchel A. et al. Function and dynamics of PKD2 in Chlamydomonas reinhardtii flagella. J. Cell Biol. 2007; 179(3): 501-14.
  70. Malicki J., Avidor-Reiss T. From the cytoplasm into the cilium: bon voyage. Organogenesis 2014; 10(1): 138-57.
  71. Lemos F.O., Ehrlich B.E. Polycystin and calcium signaling in cell death and survival. Cell Calcium 2018; 69: 37-45.
  72. Praetorius H.A., Spring K.R. The renal cell primary cilium functions as a flow sensor. Curr. Opin. Nephrol. Hypertens. 2003; 12(5): 517-20.
  73. Leyssac P.P. Changes in single nephron renin release are mediated by tubular fluid flow rate. Kidney Int. 1986; 30(3): 332-39.
  74. Praetorius H.A., Spring K.R. Bending the MDCK cell primary cilium increases intracellular calcium. J. Membr. Biol. 2001; 184(1): 71-9.
  75. Jin X., Mohieldin A.M., Muntean B.S. et al. Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli. Cell Mol. Life. Sci. 2014; 71(11): 2165-78.
  76. Phan M.N., Leddy H.A., Votta B.J. et al. Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes. Arthritis Rheum. 2009; 60(10): 3028-37.
  77. O’Conor C.J., Leddy H.A., Benefield H.C. et al. TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. Proc. Natl. Acad. Sci. USA 2014; 111(4): 1316-21.
  78. Masyuk A.I., Masyuk T.V., Splinter P.L. et al. Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling. Gastroenterology 2006; 131(3): 911-20.
  79. Yuan X., Yang S. Primary cilia and intraflagellar transport proteins in bone and cartilage. J. Dent. Res. 2016; 95(12): 1341-49.
  80. Nauli S.M, Kawanabe Y.K., Kaminski J.J. et al. Endothelial Cilia Are Fluid Shear Sensors That Regulate Calcium Signaling and Nitric Oxide Production Through Polycystin-1. Circulation 2008; 117: 1161-71.
  81. Nauli S.M., Alenghat F.J., Luo Y. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 2003; 33(2): 129-37.
  82. Nauli S.M., Zhou J. Polycystins and mechanosensation in renal and nodal cilia. Bioessays 2004; 26(8): 844-56.
  83. Chauvet V., Tian X., Husson H. et al. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J. Clin. Invest. 2004; 114(10): 1433-43.
  84. Bhunia A.K., Piontek K., Boletta A. et al. PKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell 2002; 109(2): 157-68.
  85. Shillingford J.M., Murcia N.S., Larson C.H. et al. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci USA 2006; 103(14): 5466-71.
  86. Kim E., Arnould T., Sellin L.K. et al. The polycystic kidney disease 1 gene product modulates Wnt signaling. J. Biol. Chem. 1999; 274(8): 4947-53.
  87. Arnould T., Kim E., Tsiokas L. et al. The polycystic kidney disease 1 gene product mediates protein kinase C а-dependent and c-Jun N-terminal kinase-dependent activation of the transcription factor AP-1. J. Biol. Chem. 1998; 273(11): 6013-8.
  88. Parnell S.C., Magenheimer B.S., Maser R.L. et al. Polycystin-1 activation of c-Jun N-terminal kinase and AP-1 is mediated by heterotrimeric G proteins. J. Biol. Chem. 2002; 277(22): 19566-72.
  89. Nauli S.M., Pala R., Kleene S.J. Calcium channels in primary cilia. Curr. Opin. Nephrol. Hypertens. 2016; 25(5): 452-8.
  90. Maroto R., Raso A., Wood T.G. et al. TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat. Cell Biol. 2005; 7(2): 179-85.
  91. Wann A.K.T., Zuo N., Haycraft C.J. et al. Primary cilia mediate mechanotransduction through control of ATP-induced Ca2+ signaling in compressed chondrocytes. FASEB J. 2012; 26(4): 1663-71.
  92. Bangs F., Anderson K.V. Primary cilia and mammalian hedgehog signaling. Cold Spring Harb Perspect Biol. 2017; 9(5): 1-21.
  93. Ingham P.W. Transducing Hedgehog: the story so far. EMBO J. 1998; 17(13): 3505-11.
  94. Corbit K.C., Aanstad P., Singla V. et al. Vertebrate Smoothened functions at the primary cilium Nature 2005; 437(7061): 1018-21.
  95. Wheway G., Nazlamova L., Hancock J.T. Signaling through the primary cilium. Front. Cell Dev. Biol. 2018; 6: 8.
  96. Höfer D., Drenckhahn D. Cytoskeletal differences between stereocilia of the human sperm passageway and microvilli/stereocilia in other locations. Anat. Rec. 1996; 245(1): 57-64.
  97. McPherson D.R. Sensory hair cells: an introduction to structure and physiology. Integr. Comp. Biol. 2018; 58(2): 282-300.
  98. McGrath J., Roy P., Perrin B.J. Stereocilia morphogenesis and maintenance through regulation of actin stability. Semin. Cell Dev. Biol. 2017; 65: 88-95.
  99. Falk N., Lösl M., Schröder N. et al. Specialized cilia in mammalian sensory systems. Cells 2015; 4(3): 500-19.
  100. Schwander M., Kachar B., Müller U. The cell biology of hearing. J. Cell Biol. 2010; 190(1): 9-20.
  101. Seo S., Datta P. Photoreceptor outer segment as a sink for membrane proteins: hypothesis and implications in retinal ciliopathies. Hum. Mol. Genet. 2017; 26(1): 75-82.
  102. Khanna H. Photoreceptor sensory cilium: traversing the ciliary gate. Cells 2015; 4(4): 674-86.
  103. Wheway G., Nazlamova L., Hancock J.T. Signaling through the primary cilium. Front. Cell Dev. Biol. 2018; 6: 8.
  104. Baker S.A., Kerov V. Photoreceptor inner and outer segments. Curr. Top. Membr. 2013; 72: 231-65.
  105. Mitchell D. C., Niu S.L., Litman B.J. Optimization of Receptor-G Protein Coupling by Bilayer Lipid Composition I: kinetics of rhodopsin-trasducin binding. J. Biol. Chem. 2001; 276(46): 42801-6.
  106. Leinders-Zufall T., Rand M.N., Shepherd G.M. et al. Calcium entry through cyclic nucleotide-gated channels in individual cilia of olfactory receptor cells: spatiotemporal dynamics. J. Neurosci. 1997; 17(11): 4136-48.
  107. Sulik K., Dehart D.B., langaki T. et al. Morphogenesis of the murine node and notochordal plate. Dev. Dyn. 1994; 201(3): 260-78.
  108. Okada Y., Takeda S., Tanaka Y. et al. Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination. Cell 2005; 121(4): 633-44.
  109. Komatsu Y., Mishina Y. Establishment of left-right asymmetry in vertebrate development: the node in mouse embryos. Cell Mol. Life Sci. 2013; 70(24): 4659-66.
  110. Nakaya M., Biris K., Tsukiyama T. et al. Wnt3alinks left-right determination with segmentation and anteroposterior axis elongation. Development 2005; 132(24): 5425-36.
  111. Tanaka Y., Okada Y., Hirokawa N. FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 2005; 435(7039): 172-7.
  112. Reiter J.F., Leroux M.R. Genes and molecular pathways underpinning ciliopathies. Nat. Rev. Mol. Cell Biol. 2017; 18(9): 533-47.
  113. Hildebrandt F., Benzing T., Katsanis N. Ciliopathies. N. Engl. J. Med. 2011; 364(16): 1533-43.
  114. Eliasson R., Mossberg B., Camner P. et al. The immotilecilia syndrome: a congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility. N. Engl. J. Med. 1977; 297(1): 1-6.
  115. Onoufriadis A., Paff T., Antony D. et al. Splice-site mutations in the axonemal outer dynein arm docking complex gene CCDC114 cause primary ciliary dyskinesia. Am. J. Hum. Genet. 2013; 92(1): 88-98.
  116. Frommer A., Hjeij R., Niki T. Loges et al. Immunofluorescence analysis and diagnosis of primary ciliary dyskinesia with radial spoke defects. Am. J. Respir. Cell Mol. Biol. 2015; 53(4): 563-73.
  117. Boon M., Wallmeier J., Ma L. et al. MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia. Nat. Commun. 2014; 5: 4418.
  118. Choksi S.P., Lauter G., Swoboda P. et al. Switching on cilia: transcriptional networks regulating ciliogenesis. Development 2014; 141(7): 1427-41.
  119. Wallmeier J., Frank D., Shoemark A. et al. De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left/Right Body Asymmetry. Am. J. Hum. Genet. 2019; 105(5): 1030-9.
  120. Narita K., Takeda S. Cilia in the choroid plexus: their roles in hydrocephalus and beyond. Front. Cell Neurosci. 2015; 9: 39.
  121. Liu B., Chen S., Johnson C. et al. A ciliopathy with hydrocephalus, isolated craniosynostosis, hypertelorism, and clefting caused by deletion of Kif3a. Reprod. Toxicol. 2014; 48: 88-97.
  122. Waters A.M., Beales P.L. Ciliopathies: an expanding disease spectrum. Pediatr. Nephrol. 2011; 26(7): 1039-56.
  123. Pala R., Alomari N., Nauli S.M. Primary cilium-dependent signaling mechanisms. Int. J. Mol. Sci. 2017; 18(11): 2272.
  124. Irigoin F., Badano J. Keeping the balance between proliferation and differentiation: the primary cilium. Curr. Genomics 2011; 12(4): 285-97.
  125. Wheway G., Nazlamova L., Hancock J.T. Signaling through the primary cilium. Front. Cell Dev. Biol. 2018; 6: 8.
  126. Boletta A., Qian F., Onuchic L.F. et al. Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulo-genesis in MDCK cells. Molecular cell 2000; 6(5): 1267-73.
  127. Piontek K., Menezes L.F., Garcia-Gonzalez M.A. et al. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat. Med. 2007; 13(12): 1490-5.
  128. Takakura A., Contrino L., Beck A.W. et al. Pkd1 inactivation induced in adulthood produces focal cystic disease. J. Am. Soc. Nephrol. 2008; 19(12): 2351-63.
  129. Zhang M.Z., Mai W., Li C. et al. PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells. Proc. Natl. Acad. Sci. USA 2004; 101(8): 2311-6.
  130. Ward C.J., Hogan M.C., Rossetti S. et al. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptorlike protein. Nat. Genet. 2002; 30(3): 259-69.
  131. Mai W., Chen D., Ding T. et al. Inhibition of Pkhd1 impairs tubulomorphogenesis of cultured IMCD cells. Mol. Biol. Cell 2005; 16(9): 4398-409.
  132. Dorn L., Menezes L.F, Mikuz G. et al. Immunohistochemical detection of polyductin and co-localization with liver progenitor cell markers during normal and abnormal development of the intrahepatic biliary system and in adult hepatobiliary carcinomas. J. Cell Mol. Med. 2009; 13(7): 1279-90.
  133. Sato Y., Ren X.S., Nakanuma Y. Caroli's disease: current knowledge of its biliary pathogenesis obtained from an orthologous rat model. Int. J. Hepatol. 2012; 2012: 1-10.
  134. Strazzabosco M., Fabris L. Development of the bile ducts: essentials for the clinical hepatologist. J. Hepatol. 2012; 56(5): 1159-70.
  135. Mavlikeev M., Titova A., Saitburkhanova R. et al. Caroli syndrome: a clinical case with detailed histopathological analysis. Clin. J. Gastroenterol. 2019; 12(2): 106-11.
  136. Priya S., Nampoothiri S., Sen P. et al. Bardet-Biedl syndrome: Genetics, molecular pathophysiology, and disease management. Indian J. Ophthalmol. 2016; 64(9): 620-27.
  137. Gascue C., Tan P.L., Cardenas-Rodriguez M. et al. Direct role of Bardet-Biedl syndrome proteins in transcriptional regulation. J. Cell Sci. 2012; 125(Pt 2): 362-75.
  138. Singh S., Gui M., Koh F. et al. Structure and activation mechanism of the BBSome membrane-protein trafficking complex. Elife 2020; 9: 1-22.
  139. Hua K., Ferland R.J. Primary cilia proteins: ciliary and extraciliary sites and functions. Cell Mo.l Life Sci. 2018; 75(9): 1521-40.
  140. Suspitsin E.N., Imyanitov E.N. Bardet-biedl syndrome. Mol. Syndromol. 2016; 7(2): 62-71.
  141. Yen H.J., Tayeh M.K., Mullins R.F., et al. Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function. Hum. Mol. Genet. 2006; 15(5): 667-77.
  142. Katsanis N., Lupski J.R., Beales P.L. Exploring the molecular basis of Bardet-Biedl syndrome. Hum. Mol. Genet. 2001; 10(20): 2293-9.
  143. Novas R., Cardenas-Rodriguez M., Irigoin F. et al. Bardet-Biedl syndrome: is it only cilia dysfunction? FEBS Lett. 2015; 589(22): 3479-91.
  144. Zhang Q., Seo S., Bugge K. et al. BBS proteins interact genetically with the IFT pathway to influence SHH-related phenotypes. Hum. Mol. Genet. 2012; 21(9): 1945-53.
  145. Hartill V., Szymanska K., Sharif S.M. et al. Meckel-Gruber syndrome: An update on diagnosis, clinical management, and research advances. Front. Pediatr. 2017; 5: 244.
  146. Maglic D., Stephen J., Malicdan M.C. et al. TMEM231 Gene Conversion Associated with Joubert and Meckel-Gruber Syndromes in the Same Family. Hum. Mutat. 2016; 37(11): 1144-8.
  147. Weatherbee S.D., Niswander L.A., Anderson K.V.A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling. Hum. Mol. Genet. 2009; 18(23): 4565-75.
  148. Chih B., Liu P., Chinn Y. et al. A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain. Nat. Cell Biol. 2011; 14(1): 61-72.
  149. Liu H., Kiseleva A.A., Golemis E.A. Ciliary signalling in cancer. Nat. Rev. Cancer. 2018; 18(8): 511-24.
  150. Higgins M., Obaidi I., McMorrow T. Primary cilia and their role in cancer. Oncol. Lett. 2019; 17(3): 3041-7.
  151. Wong S.Y., Seol A.D., So P.L. et al. Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat. Med. 2009; 15(9): 1055-61.
  152. Emoto K., Masugi Y., Yamazaki K. et al. Presence of primary cilia in cancer cells correlates with prognosis of pancreatic ductal adenocarcinoma. Hum. Pathol. 2014; 45(4): 817-25.
  153. Schimmack S., Kneller S., Dadabaeva N. et al. Epithelial to stromal re-distribution of primary cilia during pancreatic carcinogenesis. PLoS One 2016; 11(10): 1-16.
  154. Seeley E.S., Carrière C., Goetze T. et al. Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia. Cancer Res. 2009; 69(2): 422-30.
  155. Fabbri L., Bost F., Mazure N.M. Primary Cilium in Cancer Hallmarks. Int. J. Mol. Sci. 2019; 20(6): 1336.
  156. Bailey J. M. et al. Sonic hedgehog promotes desmoplasia in pancreatic cancer. Clin. Cancer Res. 2008;14(19): 5995-6004.
  157. Kenny T.D., Beales P.L., editors. Ciliopathies: A reference for clinicians. Oxford University Press; 2013.
  158. Oud M.M., Lamers I.J.C., Arts H.H. Ciliopathies: genetics in pediatric medicine. J. Pediatr. Genet. 2017; 6(1): 18-29.
  159. Anguela X.M., High K.A. Entering the modern era of gene therapy. Annu. Rev. Med. 2019; 70: 273-88.
  160. McIntyre J.C., Davis E.E., Joiner A. et al. Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model. Nat. Med. 2012; 18(9): 1423-8.
  161. Allergan And Editas Medicine Announce Dosing Of First Patient In Landmark Phase 1/2 Clinical Trial Of CRISPR Medicine AGN-151587 (EDIT-101) For The Treatment Of LCA10, https://ir.editasmedicine.com/news-releases/news-release-details/ allergan-and-editas-medicine-announce-dosing-first-patient.
  162. Zhou J. Polycystins and primary cilia: primers for cell cycle progression. Annu. Rev. Physiol. 2009; 71: 83-113.

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