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Primary Cilia in Cerebral Cortex: Growth and Functions on Neuronal and Non-neuronal Cells

  • Matthew R. SarkisianEmail author
  • Jon I. Arellano
  • Joshua J. Breunig
Chapter

Abstract

The prevailing view until very recently was that primary neuronal cilia, which were first described in electron microscopic studies of the central nervous system (CNS) approximately 50 years ago, were likely vestigial. This was due in large part to their lost motility during the course of evolution. For decades, further investigation into these structures was hampered by the lack of methods to specifically label cilia and the paucity of information about their growth and function in the CNS. In this chapter, we review the unexpected roles that primary cilia have in shaping the CNS and in particular the generation and maturation of cells in the postnatal cerebral cortex. We discuss newly available research tools for detecting cilia and manipulating ciliogenesis. Focusing on the mammalian cerebral cortex, this chapter reviews the patterns of growth of neuronal cilia, signaling profiles and putative functions of neuronal and non-neuronal cilia, and potential consequences of abnormal ciliogenesis in these cell types.

Keywords

Cerebral cortex Hippocampus Primary cilium Axoneme Basal body Ciliogenesis Excitatory Inhibitory Glia G protein-coupled receptor Sonic hedgehog 

References

  1. Adamantidis A, Thomas E, Foidart A, Tyhon A, Coumans B, Minet A, Tirelli E, Seutin V, Grisar T, Lakaye B (2005) Disrupting the melanin-concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function. Eur J Neurosci 21:2837–2844PubMedCrossRefGoogle Scholar
  2. Amador-Arjona A, Elliott J, Miller A, Ginbey A, Pazour GJ, Enikolopov G, Roberts AJ, Terskikh AV (2011) Primary cilia regulate proliferation of amplifying progenitors in adult hippocampus: implications for learning and memory. J Neurosci 31:9933–9944PubMedCrossRefGoogle Scholar
  3. Anastas SB, Mueller D, Semple-Rowland SL, Breunig JJ, Sarkisian MR (2011) Failed cytokinesis of neural progenitors in citron kinase-deficient rats leads to multiciliated neurons. Cereb Cortex 21:338–344PubMedCrossRefGoogle Scholar
  4. Arellano JI, Guadiana SM, Breunig JJ, Rakic P, Sarkisian MR (2012) Development and distribution of neuronal cilia in mouse neocortex. J Comp Neurol 590:848–873CrossRefGoogle Scholar
  5. Bachmann-Gagescu R, Ishak GE, Dempsey JC, Adkins J, O’Day D, Phelps IG, Gunay-Aygun M, Kline AD, Szczaluba K, Martorell L, Alswaid A, Alrasheed S, Pai S, Izatt L, Ronan A, Parisi MA, Mefford H, Glass I, Doherty D (2012) Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures. J Med Genet 49:126–137PubMedCrossRefGoogle Scholar
  6. Balordi F, Fishell G (2007) Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons. J Neurosci 27:5936–5947PubMedCrossRefGoogle Scholar
  7. Barzi M, Berenguer J, Menendez A, Alvarez-Rodriguez R, Pons S (2010) Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base. J Cell Sci 123:62–69PubMedCrossRefGoogle Scholar
  8. Belgacem YH, Borodinsky LN (2011) Sonic hedgehog signaling is decoded by calcium spike activity in the developing spinal cord. Proc Natl Acad Sci USA 108:4482–4487PubMedCrossRefGoogle Scholar
  9. Bennouna-Greene V, Kremer S, Stoetzel C, Christmann D, Schuster C, Durand M, Verloes A, Sigaudy S, Holder-Espinasse M, Godet J, Brandt C, Marion V, Danion A, Dietemann JL, Dollfus H (2011) Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet-Biedl syndrome underline complex CNS impact of primary cilia. Clin Genet 80:523–531PubMedCrossRefGoogle Scholar
  10. Berbari NF, Bishop GA, Askwith CC, Lewis JS, Mykytyn K (2007) Hippocampal neurons possess primary cilia in culture. J Neurosci Res 85:1095–1100PubMedCrossRefGoogle Scholar
  11. Berbari NF, Johnson AD, Lewis JS, Askwith CC, Mykytyn K (2008a) Identification of ciliary localization sequences within the third intracellular loop of G protein-coupled receptors. Mol Biol Cell 19:1540–1547PubMedCrossRefGoogle Scholar
  12. Berbari NF, Lewis JS, Bishop GA, Askwith CC, Mykytyn K (2008b) Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia. Proc Natl Acad Sci USA 105:4242–4246PubMedCrossRefGoogle Scholar
  13. Billingsley G, Bin J, Fieggen KJ, Duncan JL, Gerth C, Ogata K, Wodak SS, Traboulsi EI, Fishman GA, Paterson A, Chitayat D, Knueppel T, Millan JM, Mitchell GA, Deveault C, Heon E (2010) Mutations in chaperonin-like BBS genes are a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population. J Med Genet 47:453–463PubMedCrossRefGoogle Scholar
  14. 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
  15. Brailov I, Bancila M, Brisorgueil MJ, Miquel MC, Hamon M, Verge D (2000) Localization of 5-HT(6) receptors at the plasma membrane of neuronal cilia in the rat brain. Brain Res 872:271–275PubMedCrossRefGoogle Scholar
  16. Breunig JJ, Silbereis J, Vaccarino FM, Sestan N, Rakic P (2007) Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus. Proc Natl Acad Sci USA 104:20558–20563PubMedCrossRefGoogle Scholar
  17. 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
  18. Breunig JJ, Haydar TF, Rakic P (2011) Neural stem cells: historical perspective and future prospects. Neuron 70:614–625PubMedCrossRefGoogle Scholar
  19. 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
  20. Caspary T, Larkins CE, Anderson KV (2007) The graded response to sonic hedgehog depends on cilia architecture. Dev Cell 12:767–778PubMedCrossRefGoogle Scholar
  21. Chakravarthy B, Gaudet C, Menard M, Atkinson T, Chiarini A, Dal Pra I, Whitfield J (2010) The p75 neurotrophin receptor is localized to primary cilia in adult murine hippocampal dentate gyrus granule cells. Biochem Biophys Res Commun 401:458–462PubMedCrossRefGoogle Scholar
  22. Chakravarthy B, Gaudet C, Menard M, Atkinson T, Brown L, Laferla FM, Armato U, Whitfield J (2011) Amyloid-beta peptides stimulate the expression of the p75(NTR) neurotrophin receptor in SHSY5Y human neuroblastoma cells and AD transgenic mice. J Alzheimers Dis 19:915–925Google Scholar
  23. Chih B, Liu P, Chinn Y, Chalouni C, Komuves LG, Hass PE, Sandoval W, Peterson AS (2012) A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain. Nat Cell Biol 14:61–72CrossRefGoogle Scholar
  24. Corbit KC, Shyer AE, Dowdle WE, Gaulden J, Singla V, Chen MH, Chuang PT, Reiter JF (2008) Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat Cell Biol 10:70–76PubMedCrossRefGoogle Scholar
  25. D’Souza-Schorey C, Chavrier P (2006) ARF proteins: roles in membrane traffic and beyond. Nat Rev Mol Cell Biol 7:347–358PubMedCrossRefGoogle Scholar
  26. Dahl HA (1963) Fine structure of cilia in rat cerebral cortex. Z Zellforsch Mikrosk Anat 60:369–386PubMedCrossRefGoogle Scholar
  27. Davenport JR, Yoder BK (2005) An incredible decade for the primary cilium: a look at a once-forgotten organelle. Am J Physiol Renal Physiol 289:F1159–F1169PubMedCrossRefGoogle Scholar
  28. 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
  29. Del Cerro MP, Snider RS (1969) The Purkinje cell cilium. Anat Rec 165:127–130PubMedCrossRefGoogle Scholar
  30. Domire JS, Mykytyn K (2009) Markers for neuronal cilia. Methods Cell Biol 91:111–121PubMedCrossRefGoogle Scholar
  31. Domire JS, Green JA, Lee KG, Johnson AD, Askwith CC, Mykytyn K (2011) Dopamine receptor 1 localizes to neuronal cilia in a dynamic process that requires the Bardet-Biedl syndrome proteins. Cell Mol Life Sci 68:2951–2960PubMedCrossRefGoogle Scholar
  32. Dowdle WE, Robinson JF, Kneist A, Sirerol-Piquer MS, Frints SG, Corbit KC, Zaghloul NA, van Lijnschoten G, Mulders L, Verver DE, Zerres K, Reed RR, Attie-Bitach T, Johnson CA, Garcia-Verdugo JM, Katsanis N, Bergmann C, Reiter JF (2011) Disruption of a ciliary B9 protein complex causes Meckel syndrome. Am J Hum Genet 89:94–110PubMedCrossRefGoogle Scholar
  33. Einstein EB, Patterson CA, Hon BJ, Regan KA, Reddi J, Melnikoff DE, Mateer MJ, Schulz S, Johnson BN, Tallent MK (2010) Somatostatin signaling in neuronal cilia is critical for object recognition memory. J Neurosci 30:4306–4314PubMedCrossRefGoogle Scholar
  34. Fuchs JL, Schwark HD (2004) Neuronal primary cilia: a review. Cell Biol Int 28:111–118PubMedCrossRefGoogle Scholar
  35. Garcia-Gonzalo FR, Corbit KC, Sirerol-Piquer MS, Ramaswami G, Otto EA, Noriega TR, Seol AD, Robinson JF, Bennett CL, Josifova DJ, Garcia-Verdugo JM, Katsanis N, Hildebrandt F, Reiter JF (2011) A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet 43:776–784PubMedCrossRefGoogle Scholar
  36. Gascue C, Tan PL, Cardenas-Rodriguez M, Libisch G, Fernandez-Calero T, Liu YP, Astrada S, Robello C, Naya H, Katsanis N, Badano JL (2012) Direct role of Bardet-Biedl syndrome proteins in transcriptional regulation. J Cell Sci 125:362–375PubMedCrossRefGoogle Scholar
  37. Green JA, Mykytyn K (2010) Neuronal ciliary signaling in homeostasis and disease. Cell Mol Life Sci 67:3287–3297PubMedCrossRefGoogle Scholar
  38. Green JS, Parfrey PS, Harnett JD, Farid NR, Cramer BC, Johnson G, Heath O, McManamon PJ, O’Leary E, Pryse-Phillips W (1989) The cardinal manifestations of Bardet-Biedl syndrome, a form of Laurence-Moon-Biedl syndrome. N Engl J Med 321:1002–1009PubMedCrossRefGoogle Scholar
  39. Hamon M, Doucet E, Lefevre K, Miquel MC, Lanfumey L, Insausti R, Frechilla D, Del Rio J, Verge D (1999) Antibodies and antisense oligonucleotide for probing the distribution and putative functions of central 5-HT6 receptors. Neuropsychopharmacology 21:68S–76SPubMedGoogle Scholar
  40. 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
  41. Handel M, Schulz S, Stanarius A, Schreff M, Erdtmann-Vourliotis M, Schmidt H, Wolf G, Hollt V (1999) Selective targeting of somatostatin receptor 3 to neuronal cilia. Neuroscience 89:909–926PubMedCrossRefGoogle Scholar
  42. Harwell CC, Parker PR, Gee SM, Okada A, McConnell SK, Kreitzer AC, Kriegstein AR (2012) Sonic hedgehog expression in corticofugal projection neurons directs cortical microcircuit formation. Neuron 73:1116–1126PubMedCrossRefGoogle Scholar
  43. Jin H, White SR, Shida T, Schulz S, Aguiar M, Gygi SP, Bazan JF, Nachury MV (2010) The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia. Cell 141:1208–1219PubMedCrossRefGoogle Scholar
  44. Karlsson U (1966) Three-dimensional studies of neurons in the lateral geniculate nucleus of the rat. I. Organelle organization in the perikaryon and its proximal branches. J Ultrastruct Res 16:429–481PubMedCrossRefGoogle Scholar
  45. Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27:447–452PubMedCrossRefGoogle Scholar
  46. Keryer G, Pineda JR, Liot G, Kim J, Dietrich P, Benstaali C, Smith K, Cordelieres FP, Spassky N, Ferrante RJ, Dragatsis I, Saudou F (2011) Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease. J Clin Invest 121:4372–4382PubMedCrossRefGoogle Scholar
  47. 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
  48. Kumamoto N, Gu Y, Wang J, Janoschka S, Takemaru K, Levine J, Ge S (2012) A role for primary cilia in glutamatergic synaptic integration of adult-born neurons. Nat Neurosci 15:399–405PubMedCrossRefGoogle Scholar
  49. Lee JE, Gleeson JG (2011) Cilia in the nervous system: linking cilia function and neurodevelopmental disorders. Curr Opin Neurol 24:98–105PubMedCrossRefGoogle Scholar
  50. Leroux MR (2010) Tubulin acetyltransferase discovered: ciliary role in the ancestral eukaryote expanded to neurons in metazoans. Proc Natl Acad Sci USA 107:21238–21239PubMedCrossRefGoogle Scholar
  51. Li A, Saito M, Chuang JZ, Tseng YY, Dedesma C, Tomizawa K, Kaitsuka T, Sung CH (2011) Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors. Nat Cell Biol 13:402–411PubMedCrossRefGoogle Scholar
  52. Louvi A, Grove EA (2011) Cilia in the CNS: the quiet organelle claims center stage. Neuron 69:1046–1060PubMedCrossRefGoogle Scholar
  53. Lugert S, Basak O, Knuckles P, Haussler U, Fabel K, Gotz M, Haas CA, Kempermann G, Taylor V, Giachino C (2010) Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell 6:445–456PubMedCrossRefGoogle Scholar
  54. Ma X, Peterson R, Turnbull J (2012) Adenylyl cyclase type 3, a marker of primary cilia, is reduced in primary cell culture and in lumbar spinal cord in situ in G93A SOD1 mice. BMC Neurosci 12:71CrossRefGoogle Scholar
  55. Mandl L, Megele R (1989) Primary cilia in normal human neocortical neurons. Z Mikrosk Anat Forsch 103:425–430PubMedGoogle Scholar
  56. Marley A, von Zastrow M (2010) DISC1 regulates primary cilia that display specific dopamine receptors. PLoS One 5:e10902PubMedCrossRefGoogle Scholar
  57. Marshall WF, Rosenbaum JL (2001) Intraflagellar transport balances continuous turnover of outer doublet microtubules: implications for flagellar length control. J Cell Biol 155:405–414PubMedCrossRefGoogle Scholar
  58. Massinen S, Hokkanen ME, Matsson H, Tammimies K, Tapia-Paez I, Dahlstrom-Heuser V, Kuja-Panula J, Burghoorn J, Jeppsson KE, Swoboda P, Peyrard-Janvid M, Toftgard R, Castren E, Kere J (2011) Increased expression of the dyslexia candidate gene DCDC2 affects length and signaling of primary cilia in neurons. PLoS One 6:e20580PubMedCrossRefGoogle Scholar
  59. Michaud EJ, Yoder BK (2006) The primary cilium in cell signaling and cancer. Cancer Res 66:6463–6467PubMedCrossRefGoogle Scholar
  60. Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250PubMedCrossRefGoogle Scholar
  61. Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A (2008) Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3:265–278PubMedCrossRefGoogle Scholar
  62. Miyoshi K, Onishi K, Asanuma M, Miyazaki I, Diaz-Corrales FJ, Ogawa N (2006) Embryonic expression of pericentrin suggests universal roles in ciliogenesis. Dev Genes Evol 216:537–542PubMedCrossRefGoogle Scholar
  63. Miyoshi K, Kasahara K, Miyazaki I, Asanuma M (2009a) Lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Biochem Biophys Res Commun 388:757–762PubMedCrossRefGoogle Scholar
  64. Miyoshi K, Kasahara K, Miyazaki I, Shimizu S, Taniguchi M, Matsuzaki S, Tohyama M, Asanuma M (2009b) Pericentrin, a centrosomal protein related to microcephalic primordial dwarfism, is required for olfactory cilia assembly in mice. FASEB J 23:3289–3297PubMedCrossRefGoogle Scholar
  65. Moser JJ, Fritzler MJ, Rattner JB (2009) Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells. BMC Cancer 9:448PubMedCrossRefGoogle Scholar
  66. Mukhopadhyay S, Wen X, Chih B, Nelson CD, Lane WS, Scales SJ, Jackson PK (2010) TULP3 Bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia. Genes Dev 24:2180–2193PubMedCrossRefGoogle Scholar
  67. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318PubMedCrossRefGoogle Scholar
  68. Nishiyama A, Komitova M, Suzuki R, Zhu X (2009) Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10:9–22PubMedCrossRefGoogle Scholar
  69. Ou G, Blacque OE, Snow JJ, Leroux MR, Scholey JM (2005) Functional coordination of intraflagellar transport motors. Nature 436:583–587PubMedCrossRefGoogle Scholar
  70. Ou Y, Ruan Y, Cheng M, Moser JJ, Rattner JB, van der Hoorn FA (2009) Adenylate cyclase regulates elongation of mammalian primary cilia. Exp Cell Res 315:2802–2817PubMedCrossRefGoogle Scholar
  71. Palma V, Lim DA, Dahmane N, Sanchez P, Brionne TC, Herzberg CD, Gitton Y, Carleton A, Alvarez-Buylla A, Ruiz i Altaba A (2005) Sonic hedgehog controls stem cell behavior in the postnatal and adult brain. Development 132:335–344PubMedCrossRefGoogle Scholar
  72. Piperno G, Fuller MT (1985) Monoclonal antibodies specific for an acetylated form of alpha-tubulin recognize the antigen in cilia and flagella from a variety of organisms. J Cell Biol 101:2085–2094PubMedCrossRefGoogle Scholar
  73. Riobo NA, Lu K, Ai X, Haines GM, Emerson CP Jr (2006) Phosphoinositide 3-kinase and Akt are essential for Sonic Hedgehog signaling. Proc Natl Acad Sci USA 103:4505–4510PubMedCrossRefGoogle Scholar
  74. 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
  75. Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, Wong M, Gupta N, Berger MS, Huang E, Garcia-Verdugo JM, Rowitch DH, Alvarez-Buylla A (2011) Corridors of migrating neurons in the human brain and their decline during infancy. Nature 478:382–386PubMedCrossRefGoogle Scholar
  76. Santiago Ramón y Cajal (trans: Swanson N, Swanson LW) (1995) Histology of the nervous system, vols I & II. Oxford University Press, New York, pp 805– 806Google Scholar
  77. Sharma N, Kosan ZA, Stallworth JE, Berbari NF, Yoder BK (2011) Soluble levels of cytosolic tubulin regulate ciliary length control. Mol Biol Cell 22:808–816CrossRefGoogle Scholar
  78. Shida T, Cueva JG, Xu Z, Goodman MB, Nachury MV (2010) The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation. Proc Natl Acad Sci USA 107:21517–21522PubMedCrossRefGoogle Scholar
  79. Sorokin S (1962) Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells. J Cell Biol 15:363–377PubMedCrossRefGoogle Scholar
  80. Sorokin SP (1968a) Centriole formation and ciliogenesis. Aspen Emphysema Conf 11:213–216PubMedGoogle Scholar
  81. Sorokin SP (1968b) Reconstructions of centriole formation and ciliogenesis in mammalian lungs. J Cell Sci 3:207–230PubMedGoogle Scholar
  82. Sotelo JR, Trujillo-Cenoz O (1958) Electron microscope study on the development of ciliary components of the neural epithelium of the chick embryo. Z Zellforsch Mikrosk Anat 49:1–12PubMedCrossRefGoogle Scholar
  83. 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
  84. Stanic D, Malmgren H, He H, Scott L, Aperia A, Hokfelt T (2009) Developmental changes in frequency of the ciliary somatostatin receptor 3 protein. Brain Res 1249:101–112PubMedCrossRefGoogle Scholar
  85. Tissir F, Goffinet AM (2012) Cilia: conductors’ batons of neuronal maturation. Nat Neurosci 15:344–345PubMedCrossRefGoogle Scholar
  86. Town T, Breunig JJ, Sarkisian MR, Spilianakis C, Ayoub AE, Liu X, Ferrandino AF, Gallagher AR, Li MO, Rakic P, Flavell RA (2008) The stumpy gene is required for mammalian ciliogenesis. Proc Natl Acad Sci USA 105:2853–2858PubMedCrossRefGoogle Scholar
  87. Tucker RW, Pardee AB, Fujiwara K (1979a) Centriole ciliation is related to quiescence and DNA synthesis in 3T3 cells. Cell 17:527–535PubMedCrossRefGoogle Scholar
  88. Tucker RW, Scher CD, Stiles CD (1979b) Centriole deciliation associated with the early response of 3T3 cells to growth factors but not to SV40. Cell 18:1065–1072PubMedCrossRefGoogle Scholar
  89. Vincensini L, Blisnick T, Bastin P (2011) 1001 model organisms to study cilia and flagella. Biol Cell 103:109–130PubMedCrossRefGoogle Scholar
  90. Wang Z, Li V, Chan GC, Phan T, Nudelman AS, Xia Z, Storm DR (2009) Adult type 3 adenylyl cyclase-deficient mice are obese. PLoS One 4:e6979PubMedCrossRefGoogle Scholar
  91. Wang Z, Phan T, Storm DR (2011) The type 3 adenylyl cyclase is required for novel object learning and extinction of contextual memory: role of cAMP signaling in primary cilia. J Neurosci 31:5557–5561PubMedCrossRefGoogle Scholar
  92. Weatherbee SD, Niswander LA, Anderson KV (2009) A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling. Hum Mol Genet 18:4565–4575PubMedCrossRefGoogle Scholar
  93. Wheatley DN, Wang AM, Strugnell GE (1996) Expression of primary cilia in mammalian cells. Cell Biol Int 20:73–81PubMedCrossRefGoogle Scholar
  94. Whitfield JF (2004) The neuronal primary cilium – an extrasynaptic signaling device. Cell Signal 16:763–767PubMedCrossRefGoogle Scholar
  95. 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
  96. Wilson SL, Wilson JP, Wang C, Wang B, McConnell SK (2012) Primary cilia and Gli3 activity regulate cerebral cortical size. Dev Neurobiol 72:1196–1212Google Scholar
  97. Yoshimura K, Takeda S (2012) Hedgehog signaling regulates myelination in the peripheral nervous system through primary cilia. Differentiation 83:S78–S85PubMedCrossRefGoogle Scholar
  98. Yoshimura K, Kawate T, Takeda S (2011) Signaling through the primary cilium affects glial cell survival under a stressed environment. Glia 59:333–344PubMedCrossRefGoogle Scholar
  99. Zhou C, Cunningham L, Marcus AI, Li Y, Kahn RA (2006) Arl2 and Arl3 regulate different microtubule-dependent processes. Mol Biol Cell 17:2476–2487PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Matthew R. Sarkisian
    • 1
    Email author
  • Jon I. Arellano
    • 2
  • Joshua J. Breunig
    • 3
  1. 1.Department of Neuroscience, McKnight Brain InstituteUniversity of Florida College of MedicineGainesvilleUSA
  2. 2.Department of NeurobiologyYale UniversityNew HavenUSA
  3. 3.Department of Biomedical Sciences, Regenerative Medicine InstituteCedars-Sinai Medical CenterLos AngelesUSA

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