Controlling centriole numbers: Geminin family members as master regulators of centriole amplification and multiciliogenesis

Abstract

To ensure that the genetic material is accurately passed down to daughter cells during mitosis, dividing cells must duplicate their chromosomes and centrosomes once and only once per cell cycle. The same key steps—licensing, duplication, and segregation—control both the chromosome and the centrosome cycle, which must occur in concert to safeguard genome integrity. Aberrations in genome content or centrosome numbers lead to genomic instability and are linked to tumorigenesis. Such aberrations, however, can also be part of the normal life cycle of specific cell types. Multiciliated cells best exemplify the deviation from a normal centrosome cycle. They are post-mitotic cells which massively amplify their centrioles, bypassing the rule for once-per-cell-cycle centriole duplication. Hundreds of centrioles dock to the apical cell surface and generate motile cilia, whose concerted movement ensures fluid flow across epithelia. The early steps that control the generation of multiciliated cells have lately started to be elucidated. Geminin and the vertebrate-specific GemC1 and McIdas are distantly related coiled-coil proteins, initially identified as cell cycle regulators associated with the chromosome cycle. Geminin is required to ensure once-per-cell-cycle genome replication, while McIdas and GemC1 bind to Geminin and are implicated in DNA replication control. Recent findings highlight Geminin family members as early regulators of multiciliogenesis. GemC1 and McIdas specify the multiciliate cell fate by forming complexes with the E2F4/5 transcription factors to switch on a gene expression program leading to centriole amplification and cilia formation. Positive and negative interactions among Geminin family members may link cell cycle control to centriole amplification and multiciliogenesis, acting close to the point of transition from proliferation to differentiation. We review key steps of centrosome duplication and amplification, present the role of Geminin family members in the centrosome and chromosome cycle, and discuss links with disease.

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References

  1. Al Jord A, Lemaitre AI, Delgehyr N, Faucourt M, Spassky N, Meunier A (2014) Centriole amplification by mother and daughter centrioles differs in multiciliated cells. Nature 516(7529):104–107. https://doi.org/10.1038/nature13770

    PubMed  Article  CAS  Google Scholar 

  2. Amirav I, Wallmeier J, Loges NT, Menchen T, Pennekamp P, Mussaffi H, Abitbul R, Avital A, Bentur L, Dougherty GW, Nael E, Lavie M, Olbrich H, Werner C, Kintner C, Omran H, Israeli PCD Consortium Investigators (2016) Systematic analysis of CCNO variants in a defined population: implications for clinical phenotype and differential diagnosis. Hum Mutat 37(4):396–405. https://doi.org/10.1002/humu.22957

    CAS  PubMed  Article  Google Scholar 

  3. Arbi M, Pefani DE, Kyrousi C, Lalioti ME, Kalogeropoulou A, Papanastasiou AD, Taraviras S, Lygerou Z (2016) GemC1 controls multiciliogenesis in the airway epithelium. EMBO Rep 17(3):400–413. 10.15252/embr.201540882

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. Arquint C, Gabryjonczyk AM, Imseng S, Böhm R, Sauer E, Hiller S, Nigg EA, Maier T (2015) STIL binding to Polo-box 3 of PLK4 regulates centriole duplication. elife 4. https://doi.org/10.7554/eLife.07888

  5. Arquint C, Nigg EA (2014) STIL microcephaly mutations interfere with APC/C-mediated degradation and cause centriole amplification. Curr Biol 24(4):351–360. https://doi.org/10.1016/j.cub.2013.12.016

    CAS  PubMed  Article  Google Scholar 

  6. Arquint C, Nigg EA (2016) The PLK4-STIL-SAS-6 module at the core of centriole duplication. Biochem Soc Trans 44(5):1253–1263. https://doi.org/10.1042/BST20160116

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. Arquint C, Sonnen KF, Stierhof YD, Nigg EA (2012) Cell-cycle-regulated expression of STIL controls centriole number in human cells. J Cell Sci 125(5):1342–1352. https://doi.org/10.1242/jcs.099887

    CAS  PubMed  Article  Google Scholar 

  8. Baas D, Meiniel A, Benadiba C, Bonnafe E, Meiniel O, Reith W, Durand B (2006) A deficiency in RFX3 causes hydrocephalus associated with abnormal differentiation of ependymal cells. Eur J Neurosci 24(4):1020–1030. https://doi.org/10.1111/j.1460-9568.2006.05002.x

    CAS  PubMed  Article  Google Scholar 

  9. Balestra FR, Gonczy P (2014) Multiciliogenesis: multicilin directs transcriptional activation of centriole formation. Curr Biol 24(16):R746–R749. https://doi.org/10.1016/j.cub.2014.07.006

    CAS  PubMed  Article  Google Scholar 

  10. Balestrini A, Cosentino C, Errico A, Garner E, Costanzo V (2010) GEMC1 is a TopBP1-interacting protein required for chromosomal DNA replication. Nat Cell Biol 12(5):484–491. https://doi.org/10.1038/ncb2050

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  11. Bicknell LS, Bongers EM, Leitch A et al (2011a) Mutations in the pre-replication complex cause Meier-Gorlin syndrome. Nat Genet 43(4):356–359. https://doi.org/10.1038/ng.775

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. Bicknell LS, Walker S, Klingseisen A, Stiff T, Leitch A, Kerzendorfer C, Martin CA, Yeyati P, al Sanna N, Bober M, Johnson D, Wise C, Jackson AP, O’Driscoll M, Jeggo PA (2011b) Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. Nat Genet 43(4):350–355. https://doi.org/10.1038/ng.776

    CAS  PubMed  Article  Google Scholar 

  13. Blow JJ, Gillespie PJ (2008) Replication licensing and cancer—a fatal entanglement? Nat Rev Cancer 8(10):799–806. https://doi.org/10.1038/nrc2500

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. Bond J, Roberts E, Springell K, Lizarraga S, Scott S, Higgins J, Hampshire DJ, Morrison EE, Leal GF, Silva EO, Costa SMR, Baralle D, Raponi M, Karbani G, Rashid Y, Jafri H, Bennett C, Corry P, Walsh CA, Woods CG (2005) A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet 37(4):353–355. https://doi.org/10.1038/ng1539

    CAS  PubMed  Article  Google Scholar 

  15. Boon M, Wallmeier J, Ma L, Loges NT, Jaspers M, Olbrich H, Dougherty GW, Raidt J, Werner C, Amirav I, Hevroni A, Abitbul R, Avital A, Soferman R, Wessels M, O’Callaghan C, Chung EM, Rutman A, Hirst RA, Moya E, Mitchison HM, van Daele S, de Boeck K, Jorissen M, Kintner C, Cuppens H, Omran H (2014) MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia. Nat Commun 5:4418. https://doi.org/10.1038/ncomms5418

    CAS  PubMed  Article  Google Scholar 

  16. Brito DA, Gouveia SM, Bettencourt-Dias M (2012) Deconstructing the centriole: structure and number control. Curr Opin Cell Biol 24(1):4–13. https://doi.org/10.1016/j.ceb.2012.01.003

    CAS  PubMed  Article  Google Scholar 

  17. Brody SL, Yan XH, Wuerffel MK, Song SK, Shapiro SD (2000) Ciliogenesis and left-right axis defects in forkhead factor HFH-4-null mice. Am J Respir Cell Mol Biol 23(1):45–51. https://doi.org/10.1165/ajrcmb.23.1.4070

    CAS  PubMed  Article  Google Scholar 

  18. Brooks ER, Wallingford JB (2014) Multiciliated cells. Curr Biol 24(19):R973–R982. https://doi.org/10.1016/j.cub.2014.08.047

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. Brown NJ, Marjanovic M, Luders J, Stracker TH, Costanzo V (2013) Cep63 and cep152 cooperate to ensure centriole duplication. PLoS One 8(7):e69986. https://doi.org/10.1371/journal.pone.0069986

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Burrage LC, Charng WL, Eldomery MK, Willer JR, Davis EE, Lugtenberg D, Zhu W, Leduc MS, Akdemir ZC, Azamian M, Zapata G, Hernandez PP, Schoots J, de Munnik SA, Roepman R, Pearring JN, Jhangiani S, Katsanis N, Vissers LELM, Brunner HG, Beaudet a, Rosenfeld JA, Muzny DM, Gibbs RA, Eng CM, Xia F, Lalani SR, Lupski JR, Bongers EMHF, Yang Y (2015) De novo GMNN mutations cause autosomal-dominant primordial dwarfism associated with Meier-Gorlin syndrome. Am J Hum Genet 97(6):904–913. https://doi.org/10.1016/j.ajhg.2015.11.006

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. Caillat C, Fish A, Pefani DE, Taraviras S, Lygerou Z, Perrakis A (2015) The structure of the GemC1 coiled coil and its interaction with the Geminin family of coiled-coil proteins. Acta Crystallogr D Biol Crystallogr 71(11):2278–2286. https://doi.org/10.1107/S1399004715016892

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. Caillat C, Pefani DE, Gillespie PJ, Taraviras S, Blow JJ, Lygerou Z, Perrakis A (2013) The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing. J Biol Chem 288(44):31624–31634. https://doi.org/10.1074/jbc.M113.491928

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. Campbell EP, Quigley IK, Kintner C (2016) Foxn4 promotes gene expression required for the formation of multiple motile cilia. Development 143(24):4654–4664. https://doi.org/10.1242/dev.143859

    CAS  PubMed  Article  Google Scholar 

  24. Chung MI, Kwon T, Tu F, Brooks ER, Gupta R, Meyer M, Baker JC, Marcotte EM, Wallingford JB (2014) Coordinated genomic control of ciliogenesis and cell movement by RFX2. elife 3:e01439. https://doi.org/10.7554/eLife.01439

    PubMed  PubMed Central  Article  Google Scholar 

  25. Chung MI, Peyrot SM, LeBoeuf S, Park TJ, McGary KL, Marcotte EM, Wallingford JB (2012) RFX2 is broadly required for ciliogenesis during vertebrate development. Dev Biol 363(1):155–165. https://doi.org/10.1016/j.ydbio.2011.12.029

    CAS  PubMed  Article  Google Scholar 

  26. Claycomb JM, Orr-Weaver TL (2005) Developmental gene amplification: insights into DNA replication and gene expression. Trends Genet 21(3):149–162. https://doi.org/10.1016/j.tig.2005.01.009

    CAS  PubMed  Article  Google Scholar 

  27. Cunha-Ferreira I, Bento I, Pimenta-Marques A, Jana SC, Lince-Faria M, Duarte P, Borrego-Pinto J, Gilberto S, Amado T, Brito D, Rodrigues-Martins A, Debski J, Dzhindzhev N, Bettencourt-Dias M (2013) Regulation of autophosphorylation controls PLK4 self-destruction and centriole number. Curr Biol 23(22):2245–2254. https://doi.org/10.1016/j.cub.2013.09.037

    CAS  PubMed  Article  Google Scholar 

  28. Cunha-Ferreira I, Rodrigues-Martins A, Bento I, Riparbelli M, Zhang W, Laue E, Callaini G, Glover DM, Bettencourt-Dias M (2009) The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4. Curr Biol 19(1):43–49. https://doi.org/10.1016/j.cub.2008.11.037

    CAS  PubMed  Article  Google Scholar 

  29. De Marco V, Gillespie PJ, Li A, Karantzelis N, Christodoulou E, Klompmaker R, van Gerwen S, Fish A, Petoukhov MV, Iliou MS, Lygerou Z, Medema RH, Blow JJ, Svergun d, Taraviras S, Perrakis A (2009) Quaternary structure of the human Cdt1-Geminin complex regulates DNA replication licensing. Proc Natl Acad Sci U S A 106(47):19807–19812. https://doi.org/10.1073/pnas.0905281106

    PubMed  PubMed Central  Article  Google Scholar 

  30. Deblandre GA, Wettstein DA, Koyano-Nakagawa N, Kintner C (1999) A two-step mechanism generates the spacing pattern of the ciliated cells in the skin of Xenopus embryos. Development 126(21):4715–4728

    CAS  PubMed  Google Scholar 

  31. Del Bene F, Tessmar-Raible K, Wittbrodt J (2004) Direct interaction of geminin and Six3 in eye development. Nature 427(6976):745–749. https://doi.org/10.1038/nature02292

    PubMed  Article  CAS  Google Scholar 

  32. Didon L, Zwick RK, Chao IW, Walters MS, Wang R, Hackett NR, Crystal RG (2013) RFX3 modulation of FOXJ1 regulation of cilia genes in the human airway epithelium. Respir Res 14(1):70. https://doi.org/10.1186/1465-9921-14-70

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. Dimaki M, Xouri G, Symeonidou IE, Sirinian C, Nishitani H, Taraviras S, Lygerou Z (2013) Cell cycle-dependent subcellular translocation of the human DNA licensing inhibitor geminin. J Biol Chem 288(33):23953–23963. https://doi.org/10.1074/jbc.M113.453092

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Dzhindzhev NS, Tzolovsky G, Lipinszki Z, Schneider S, Lattao R, Fu J, Debski J, Dadlez M, Glover DM (2014) Plk4 phosphorylates Ana2 to trigger Sas6 recruitment and procentriole formation. Curr Biol 24(21):2526–2532. https://doi.org/10.1016/j.cub.2014.08.061

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. El Zein L, Ait-Lounis A, Morle L, Thomas J, Chhin B, Spassky N, Reith W, Durand B (2009) RFX3 governs growth and beating efficiency of motile cilia in mouse and controls the expression of genes involved in human ciliopathies. J Cell Sci 122(17):3180–3189. https://doi.org/10.1242/jcs.048348

    PubMed  Article  CAS  Google Scholar 

  36. Fenwick AL, Kliszczak M, Cooper F, Murray J, Sanchez-Pulido L, Twigg SR, Goriely A, McGowan SJ, Miller KA, Taylor IB, Logan C, WGS500 Consortium, Bozdogan S, Danda S, Dixon J, Elsayed SM, Elsobky E, Gardham A, Hoffer MJ, Koopmans M, McDonald-McGinn DM, Santen GW, Savarirayan R, de Silva D, Vanakker O, Wall SA, Wilson LC, Yuregir OO, Zackai EH, Ponting CP, Jackson AP, Wilkie AO, Niedzwiedz W, Bicknell LS (2016) Mutations in CDC45, encoding an essential component of the pre-initiation complex, cause Meier-Gorlin syndrome and craniosynostosis. Am J Hum Genet 99(1):125–138. https://doi.org/10.1016/j.ajhg.2016.05.019

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Ferguson RL, Maller JL (2008) Cyclin E-dependent localization of MCM5 regulates centrosome duplication. J Cell Sci 121(19):3224–3232. https://doi.org/10.1242/jcs.034702

    CAS  PubMed  Article  Google Scholar 

  38. Ferguson RL, Pascreau G, Maller JL (2010) The cyclin A centrosomal localization sequence recruits MCM5 and Orc1 to regulate centrosome reduplication. J Cell Sci 123(16):2743–2749. https://doi.org/10.1242/jcs.073098

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. Firat-Karalar EN, Stearns T (2014) The centriole duplication cycle. Philos Trans R Soc Lond Ser B Biol Sci 369

  40. Fragkos M, Ganier O, Coulombe P, Mechali M (2015) DNA replication origin activation in space and time. Nat Rev Mol Cell Biol 16(6):360–374. https://doi.org/10.1038/nrm4002

    CAS  PubMed  Article  Google Scholar 

  41. Fu J, Hagan IM, Glover DM (2015) The centrosome and its duplication cycle. Cold Spring Harb Perspect Biol 7(2):a015800. https://doi.org/10.1101/cshperspect.a015800

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  42. Funk MC, Bera AN, Menchen T, Kuales G, Thriene K, Lienkamp SS, Dengjel J, Omran H, Frank M, Arnold SJ (2015) Cyclin O (Ccno) functions during deuterosome-mediated centriole amplification of multiciliated cells. EMBO J 34(8):1078–1089. 10.15252/embj.201490805

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. Gao X, Bali AS, Randell SH, Hogan BL (2015) GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells. J Cell Biol 211(3):669–682. https://doi.org/10.1083/jcb.201506014

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. Gao X, Vockley CM, Pauli F, Newberry KM, Xue Y, Randell SH, Reddy t, Hogan BLM (2013) Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium.[corrected]. Proc Natl Acad Sci U S A 110(23):9356–9361. https://doi.org/10.1073/pnas.1307589110

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. Geng Y, Yu Q, Sicinska E, Das M, Schneider JE, Bhattacharya S, Rideout WM III, Bronson RT, Gardner H, Sicinski P (2003) Cyclin E ablation in the mouse. Cell 114(4):431–443. https://doi.org/10.1016/S0092-8674(03)00645-7

    CAS  PubMed  Article  Google Scholar 

  46. Gonczy P (2012) Towards a molecular architecture of centriole assembly. Nat Rev Mol Cell Biol 13(7):425–435. https://doi.org/10.1038/nrm3373

    PubMed  Article  CAS  Google Scholar 

  47. Gonczy P (2015) Centrosomes and cancer: revisiting a long-standing relationship. Nat Rev Cancer 15(11):639–652. https://doi.org/10.1038/nrc3995

    CAS  PubMed  Article  Google Scholar 

  48. Gonzalez MA, Tachibana KE, Adams DJ, van der Weyden L, Hemberger M, Coleman N, Bradley A, Laskey RA (2006) Geminin is essential to prevent endoreduplication and to form pluripotent cells during mammalian development. Genes Dev 20(14):1880–1884. https://doi.org/10.1101/gad.379706

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. Griffith E, Walker S, Martin CA, Vagnarelli P, Stiff T, Vernay B, Sanna NA, Saggar A, Hamel B, Earnshaw WC, Jeggo PA, Jackson AP, O’Driscoll M (2008) Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling. Nat Genet 40(2):232–236. https://doi.org/10.1038/ng.2007.80

    CAS  PubMed  Article  Google Scholar 

  50. Guderian G, Westendorf J, Uldschmid A, Nigg EA (2010) Plk4 trans-autophosphorylation regulates centriole number by controlling betaTrCP-mediated degradation. J Cell Sci 123(13):2163–2169. https://doi.org/10.1242/jcs.068502

    CAS  PubMed  Article  Google Scholar 

  51. Guernsey DL, Matsuoka M, Jiang H, Evans S, Macgillivray C, Nightingale M, Perry S, Ferguson M, LeBlanc M, Paquette J, Patry L, Rideout a, Thomas A, Orr A, McMaster CR, Michaud JL, Deal C, Langlois S, Superneau DW, Parkash S, Ludman M, Skidmore DL, Samuels ME (2011) Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome. Nat Genet 43(4):360–364. https://doi.org/10.1038/ng.777

    CAS  PubMed  Article  Google Scholar 

  52. Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA (2005) The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol 7(11):1140–1146. https://doi.org/10.1038/ncb1320

    CAS  PubMed  Article  Google Scholar 

  53. Hemerly AS, Prasanth SG, Siddiqui K, Stillman B (2009) Orc1 controls centriole and centrosome copy number in human cells. Science 323(5915):789–793. https://doi.org/10.1126/science.1166745

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. Hinchcliffe EH, Li C, Thompson EA, Maller JL, Sluder G (1999) Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts. Science 283(5403):851–854. https://doi.org/10.1126/science.283.5403.851

    CAS  PubMed  Article  Google Scholar 

  55. Holland AJ, Fachinetti D, Zhu Q, Bauer M, Verma IM, Nigg EA, Cleveland DW (2012) The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle. Genes Dev 26(24):2684–2689. https://doi.org/10.1101/gad.207027.112

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. Holland AJ, Lan W, Niessen S, Hoover H, Cleveland DW (2010) Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability. J Cell Biol 188(2):191–198. https://doi.org/10.1083/jcb.200911102

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. Hossain M, Stillman B (2012) Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication. Genes Dev 26(16):1797–1810. https://doi.org/10.1101/gad.197178.112

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. Huang S, Ma J, Liu X, Zhang Y, Luo L (2011) Geminin is required for left-right patterning through regulating Kupffer’s vesicle formation and ciliogenesis in zebrafish. Biochem Biophys Res Commun 410(2):164–169. https://doi.org/10.1016/j.bbrc.2011.04.085

    CAS  PubMed  Article  Google Scholar 

  59. Huang YY, Kaneko KJ, Pan H, DePamphilis ML (2015) Geminin is essential to prevent DNA re-replication-dependent apoptosis in pluripotent cells, but not in differentiated cells. Stem Cells 33(11):3239–3253. https://doi.org/10.1002/stem.2092

    CAS  PubMed  Article  Google Scholar 

  60. Iliou MS, Kotantaki P, Karamitros D, Spella M, Taraviras S, Lygerou Z (2013) Reduced Geminin levels promote cellular senescence. Mech Ageing Dev 134(1-2):10–23. https://doi.org/10.1016/j.mad.2012.10.001

    CAS  PubMed  Article  Google Scholar 

  61. Ishikawa H, Marshall WF (2011) Ciliogenesis: building the cell’s antenna. Nat Rev Mol Cell Biol 12(4):222–234. https://doi.org/10.1038/nrm3085

    CAS  PubMed  Article  Google Scholar 

  62. Karamitros D, Kotantaki P, Lygerou Z, Veiga-Fernandes H, Pachnis V, Kioussis D, Taraviras S (2010a) Differential geminin requirement for proliferation of thymocytes and mature T cells. J Immunol 184(5):2432–2441. https://doi.org/10.4049/jimmunol.0901983

    CAS  PubMed  Article  Google Scholar 

  63. Karamitros D, Kotantaki P, Lygerou Z, Veiga-Fernandes H, Pachnis V, Kioussis D, Taraviras S (2010b) Life without geminin. Cell Cycle 9(16):3181–3185. https://doi.org/10.4161/cc.9.16.12554

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. Karamitros D, Patmanidi AL, Kotantaki P, Potocnik AJ, Bahr-Ivacevic T, Benes V, Lygerou Z, Kioussis D, Taraviras S (2015) Geminin deletion increases the number of fetal hematopoietic stem cells by affecting the expression of key transcription factors. Development 142(1):70–81. https://doi.org/10.1242/dev.109454

    CAS  PubMed  Article  Google Scholar 

  65. Kim J, Lee K, Rhee K (2015) PLK1 regulation of PCNT cleavage ensures fidelity of centriole separation during mitotic exit. Nat Commun 6:10076. https://doi.org/10.1038/ncomms10076

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA (2007) Plk4-induced centriole biogenesis in human cells. Dev Cell 13(2):190–202. https://doi.org/10.1016/j.devcel.2007.07.002

    CAS  PubMed  Article  Google Scholar 

  67. Klos Dehring DA, Vladar EK, Werner ME, Mitchell JW, Hwang P, Mitchell BJ (2013) Deuterosome-mediated centriole biogenesis. Dev Cell 27(1):103–112. https://doi.org/10.1016/j.devcel.2013.08.021

    CAS  PubMed  Article  Google Scholar 

  68. Klotz-Noack K, McIntosh D, Schurch N, Pratt N, Blow JJ (2012) Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation. J Cell Sci 125(10):2436–2445. https://doi.org/10.1242/jcs.100883

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. Kratz AS, Barenz F, Richter KT, Hoffmann I (2015) Plk4-dependent phosphorylation of STIL is required for centriole duplication. Biol Open 4(3):370–377. https://doi.org/10.1242/bio.201411023

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. Kroll KL, Salic AN, Evans LM, Kirschner MW (1998) Geminin, a neuralizing molecule that demarcates the future neural plate at the onset of gastrulation. Development 125(16):3247–3258

    CAS  PubMed  Google Scholar 

  71. Kumar A, Girimaji SC, Duvvari MR, Blanton SH (2009) Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly. Am J Hum Genet 84(2):286–290. https://doi.org/10.1016/j.ajhg.2009.01.017

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. Kuo AJ, Song J, Cheung P, Ishibe-Murakami S, Yamazoe S, Chen JK, Patel DJ, Gozani O (2012) The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome. Nature 484(7392):115–119. https://doi.org/10.1038/nature10956

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  73. Kyrousi C, Arbi M, Pilz GA, Pefani d, Lalioti ME, Ninkovic J, Go tz M, Lygerou Z, Taraviras S (2015) Mcidas and GemC1 are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche. Development 142(21):3661–3674. https://doi.org/10.1242/dev.126342

    CAS  PubMed  Article  Google Scholar 

  74. Kyrousi C, Lalioti ME, Skavatsou E, Lygerou Z, Taraviras S (2016) Mcidas and GemC1/Lynkeas specify embryonic radial glial cells. Neurogenesis (Austin) 3(1):e1172747. https://doi.org/10.1080/23262133.2016.1172747

    Article  CAS  Google Scholar 

  75. Kyrousi C, Lygerou Z, Taraviras S (2017) How a radial glial cell decides to become a multiciliated ependymal cell. Glia

  76. Lacey KR, Jackson PK, Stearns T (1999) Cyclin-dependent kinase control of centrosome duplication. Proc Natl Acad Sci U S A 96(6):2817–2822. https://doi.org/10.1073/pnas.96.6.2817

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. Lee C, Hong B, Choi JM et al (2004) Structural basis for inhibition of the replication licensing factor Cdt1 by geminin. Nature 430(7002):913–917. https://doi.org/10.1038/nature02813

    CAS  PubMed  Article  Google Scholar 

  78. Lee HO, Davidson JM, Duronio RJ (2009) Endoreplication: polyploidy with purpose. Genes Dev 23(21):2461–2477. https://doi.org/10.1101/gad.1829209

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. Lee K, Rhee K (2012) Separase-dependent cleavage of pericentrin B is necessary and sufficient for centriole disengagement during mitosis. Cell Cycle 11(13):2476–2485. https://doi.org/10.4161/cc.20878

    CAS  PubMed  Article  Google Scholar 

  80. Leidel S, Delattre M, Cerutti L, Baumer K, Gonczy P (2005) SAS-6 defines a protein family required for centrosome duplication in C. elegans and in human cells. Nat Cell Biol 7(2):115–125. https://doi.org/10.1038/ncb1220

    CAS  PubMed  Article  Google Scholar 

  81. Liu Y, Pathak N, Kramer-Zucker A, Drummond IA (2007) Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros. Development 134(6):1111–1122. https://doi.org/10.1242/dev.02806

    CAS  PubMed  Article  Google Scholar 

  82. Lopes CA, Jana SC, Cunha-Ferreira I et al (2015) PLK4 trans-autoactivation controls centriole biogenesis in space. Dev Cell 35(2):222–235. https://doi.org/10.1016/j.devcel.2015.09.020

    CAS  PubMed  Article  Google Scholar 

  83. Lu F, Lan R, Zhang H, Jiang Q, Zhang C (2009) Geminin is partially localized to the centrosome and plays a role in proper centrosome duplication. Biol Cell 101(5):273–285. https://doi.org/10.1042/BC20080109

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. Luo L, Yang X, Takihara Y, Knoetgen H, Kessel M (2004) The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions. Nature 427(6976):749–753. https://doi.org/10.1038/nature02305

    CAS  PubMed  Article  Google Scholar 

  85. Lutzmann M, Maiorano D, Mechali M (2006) A Cdt1-geminin complex licenses chromatin for DNA replication and prevents rereplication during S phase in Xenopus. EMBO J 25(24):5764–5774. https://doi.org/10.1038/sj.emboj.7601436

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  86. Lygerou Z, Nurse P (2000) Cell cycle. License withheld—geminin blocks DNA replication. Science 290(5500):2271–2273

    CAS  PubMed  Google Scholar 

  87. Ma L, Quigley I, Omran H, Kintner C (2014) Multicilin drives centriole biogenesis via E2f proteins. Genes Dev 28(13):1461–1471. https://doi.org/10.1101/gad.243832.114

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  88. Marcet B, Chevalier B, Luxardi G, Coraux C, Zaragosi LE, Cibois M, Robbe-Sermesant K, Jolly T, Cardinaud B, Moreilhon C, Giovannini-Chami L, Nawrocki-Raby B, Birembaut P, Waldmann R, Kodjabachian L, Barbry P (2011) Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway. Nat Cell Biol 13(6):693–699. https://doi.org/10.1038/ncb2241

    CAS  PubMed  Article  Google Scholar 

  89. Markey M, Siddiqui H, Knudsen ES (2004) Geminin is targeted for repression by the retinoblastoma tumor suppressor pathway through intragenic E2F sites. J Biol Chem 279(28):29255–29262. https://doi.org/10.1074/jbc.M313482200

    CAS  PubMed  Article  Google Scholar 

  90. Marshall CB, Mays DJ, Beeler JS, Rosenbluth JM, Boyd KL, Santos Guasch GL, Shaver TM, Tang LJ, Liu Q, Shyr Y, Venters BJ, Magnuson MA, Pietenpol JA (2016) p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network. Cell Rep 14(10):2289–2300. https://doi.org/10.1016/j.celrep.2016.02.035

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. Marthiens V, Rujano MA, Pennetier C, Tessier S, Paul-Gilloteaux P, Basto R (2013) Centrosome amplification causes microcephaly. Nat Cell Biol 15(7):731–740. https://doi.org/10.1038/ncb2746

    CAS  PubMed  Article  Google Scholar 

  92. Martin CA, Ahmad I, Klingseisen A, Hussain MS, Bicknell LS, Leitch A, Nürnberg G, Toliat MR, Murray JE, Hunt D, Khan F, Ali Z, Tinschert S, Ding J, Keith C, Harley ME, Heyn P, Müller R, Hoffmann I, Daire VC, Dollfus H, Dupuis L, Bashamboo A, McElreavey K, Kariminejad A, Mendoza-Londono R, Moore AT, Saggar A, Schlechter C, Weleber R, Thiele H, Altmüller J, Höhne W, Hurles ME, Noegel AA, Baig SM, Nürnberg P, Jackson AP (2014) Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat Genet 46(12):1283–1292. https://doi.org/10.1038/ng.3122

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. Matsumoto Y, Hayashi K, Nishida E (1999) Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells. Curr Biol 9(8):429–432. https://doi.org/10.1016/S0960-9822(99)80191-2

    CAS  PubMed  Article  Google Scholar 

  94. Matsuo K, Ohsumi K, Iwabuchi M, Kawamata T, Ono Y, Takahashi M (2012) Kendrin is a novel substrate for separase involved in the licensing of centriole duplication. Curr Biol 22(10):915–921. https://doi.org/10.1016/j.cub.2012.03.048

    CAS  PubMed  Article  Google Scholar 

  95. McGarry TJ, Kirschner MW (1998) Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell 93(6):1043–1053. https://doi.org/10.1016/S0092-8674(00)81209-X

    CAS  PubMed  Article  Google Scholar 

  96. Melixetian M, Ballabeni A, Masiero L, Gasparini P, Zamponi R, Bartek J, Lukas J, Helin K (2004) Loss of geminin induces rereplication in the presence of functional p53. J Cell Biol 165(4):473–482. https://doi.org/10.1083/jcb.200403106

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  97. Meraldi P, Lukas J, Fry AM, Bartek J, Nigg EA (1999) Centrosome duplication in mammalian somatic cells requires E2F and Cdk2-cyclin a. Nat Cell Biol 1(2):88–93. https://doi.org/10.1038/10054

    CAS  PubMed  Article  Google Scholar 

  98. Meunier A, Azimzadeh J (2016) Multiciliated cells in animals. Cold Spring Harb Perspect Biol 8(12). https://doi.org/10.1101/cshperspect.a028233

  99. Meunier A, Spassky N (2016) Centriole continuity: out with the new, in with the old. Curr Opin Cell Biol 38:60–67. https://doi.org/10.1016/j.ceb.2016.02.007

    CAS  PubMed  Article  Google Scholar 

  100. Mori M, Hazan R, Danielian PS, Mahoney JE, Li H, Lu J, Miller ES, Zhu X, Lees JA, Cardoso WV (2017) Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis. Nat Commun 8:15857. https://doi.org/10.1038/ncomms15857

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  101. Mori M, Mahoney JE, Stupnikov MR, Paez-Cortez JR, Szymaniak AD, Varelas X, Herrick DB, Schwob J, Zhang H, Cardoso WV (2015) Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors. Development 142(2):258–267. https://doi.org/10.1242/dev.116855

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  102. Morimoto M, Nishinakamura R, Saga Y, Kopan R (2012) Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells. Development 139(23):4365–4373. https://doi.org/10.1242/dev.083840

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  103. Moyer TC, Clutario KM, Lambrus BG, Daggubati V, Holland AJ (2015) Binding of STIL to Plk4 activates kinase activity to promote centriole assembly. J Cell Biol 209(6):863–878. https://doi.org/10.1083/jcb.201502088

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  104. Nakamura T, Saito H, Takekawa M (2013) SAPK pathways and p53 cooperatively regulate PLK4 activity and centrosome integrity under stress. Nat Commun 4:1775. https://doi.org/10.1038/ncomms2752

    PubMed  Article  CAS  Google Scholar 

  105. Nano M, Basto R (2017) Consequences of centrosome dysfunction during brain development. Adv Exp Med Biol 1002:19–45. https://doi.org/10.1007/978-3-319-57127-0_2

    PubMed  Article  Google Scholar 

  106. Nemajerova A, Kramer D, Siller SS, Herr C, Shomroni O, Pena T, Gallinas Suazo C, Glaser K, Wildung M, Steffen H, Sriraman A, Oberle F, Wienken M, Hennion M, Vidal R, Royen B, Alevra M, Schild D, Bals R, Dönitz J, Riedel D, Bonn S, Takemaru KI, Moll UM, Lizé M (2016) TAp73 is a central transcriptional regulator of airway multiciliogenesis. Genes Dev 30(11):1300–1312. https://doi.org/10.1101/gad.279836.116

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  107. Nigg EA, Stearns T (2011) The centrosome cycle: centriole biogenesis, duplication and inherent asymmetries. Nat Cell Biol 13(10):1154–1160. https://doi.org/10.1038/ncb2345

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  108. Nordman J, Orr-Weaver TL (2012) Regulation of DNA replication during development. Development 139(3):455–464. https://doi.org/10.1242/dev.061838

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  109. Ohta M, Ashikawa T, Nozaki Y, Kozuka-Hata H, Goto H, Inagaki M, Oyama M, Kitagawa D (2014) Direct interaction of Plk4 with STIL ensures formation of a single procentriole per parental centriole. Nat Commun 5:5267. https://doi.org/10.1038/ncomms6267

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  110. Ortega S, Prieto I, Odajima J, Martín A, Dubus P, Sotillo R, Barbero JL, Malumbres M, Barbacid M (2003) Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet 35(1):25–31. https://doi.org/10.1038/ng1232

    CAS  PubMed  Article  Google Scholar 

  111. Pagan JK, Marzio A, Jones MJ, Saraf A, Jallepalli PV, Florens L, Washburn MP, Pagano M (2015) Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing. Nat Cell Biol 17(1):31–43. https://doi.org/10.1038/ncb3076

    CAS  PubMed  Article  Google Scholar 

  112. Papanayotou C, Mey A, Birot AM, Saka Y, Boast S, Smith JC, Samarut J, Stern CD (2008) A mechanism regulating the onset of Sox2 expression in the embryonic neural plate. PLoS Biol 6(1):e2. https://doi.org/10.1371/journal.pbio.0060002

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  113. Parisi T, Beck AR, Rougier N, McNeil T, Lucian L, Werb Z, Amati B (2003) Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cells. EMBO J 22(18):4794–4803. https://doi.org/10.1093/emboj/cdg482

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  114. Patmanidi AL, Champeris Tsaniras S, Karamitros D, Kyrousi C, Lygerou Z, Taraviras S (2017) Concise review: Geminin—a tale of two tails: DNA replication and transcriptional/epigenetic regulation in stem cells. Stem Cells 35:299–310

    CAS  PubMed  Article  Google Scholar 

  115. Patterson ES, Waller LE, Kroll KL (2014) Geminin loss causes neural tube defects through disrupted progenitor specification and neuronal differentiation. Dev Biol 393(1):44–56. https://doi.org/10.1016/j.ydbio.2014.06.021

    CAS  PubMed  Article  Google Scholar 

  116. Pefani DE, Dimaki M, Spella M, Karantzelis N, Mitsiki E, Kyrousi C, Symeonidou IE, Perrakis A, Taraviras S, Lygerou Z (2011) Idas, a novel phylogenetically conserved geminin-related protein, binds to geminin and is required for cell cycle progression. J Biol Chem 286(26):23234–23246. https://doi.org/10.1074/jbc.M110.207688

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  117. Piasecki BP, Burghoorn J, Swoboda P (2010) Regulatory Factor X (RFX)-mediated transcriptional rewiring of ciliary genes in animals. Proc Natl Acad Sci U S A 107(29):12969–12974. https://doi.org/10.1073/pnas.0914241107

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  118. Quigley IK, Kintner C (2017) Rfx2 stabilizes Foxj1 binding at chromatin loops to enable multiciliated cell gene expression. PLoS Genet 13(1):e1006538. https://doi.org/10.1371/journal.pgen.1006538

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  119. Rauch A, Thiel CT, Schindler D, Wick U, Crow YJ, Ekici AB, van Essen AJ, Goecke TO, al-Gazali L, Chrzanowska KH, Zweier C, Brunner HG, Becker K, Curry CJ, Dallapiccola B, Devriendt K, Dorfler A, Kinning E, Megarbane A, Meinecke P, Semple RK, Spranger S, Toutain A, Trembath RC, Voss E, Wilson L, Hennekam R, de Zegher F, Dorr HG, Reis A (2008) Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science 319(5864):816–819. https://doi.org/10.1126/science.1151174

    CAS  PubMed  Article  Google Scholar 

  120. Rodrigues-Martins A, Riparbelli M, Callaini G, Glover DM, Bettencourt-Dias M (2007) Revisiting the role of the mother centriole in centriole biogenesis. Science 316(5827):1046–1050. https://doi.org/10.1126/science.1142950

    CAS  PubMed  Article  Google Scholar 

  121. Rogers GC, Rusan NM, Roberts DM, Peifer M, Rogers SL (2009) The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. J Cell Biol 184(2):225–239. https://doi.org/10.1083/jcb.200808049

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  122. Roukos V, Iliou MS, Nishitani H, Gentzel M, Wilm M, Taraviras S, Lygerou Z (2007) Geminin cleavage during apoptosis by caspase-3 alters its binding ability to the SWI/SNF subunit Brahma. J Biol Chem 282(13):9346–9357. https://doi.org/10.1074/jbc.M611643200

    CAS  PubMed  Article  Google Scholar 

  123. Seo S, Herr A, Lim JW, Richardson GA, Richardson H, Kroll KL (2005) Geminin regulates neuronal differentiation by antagonizing Brg1 activity. Genes Dev 19(14):1723–1734. https://doi.org/10.1101/gad.1319105

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  124. Shinnick KM, Eklund EA, McGarry TJ (2010) Geminin deletion from hematopoietic cells causes anemia and thrombocytosis in mice. J Clin Invest 120(12):4303–4315. https://doi.org/10.1172/JCI43556

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  125. Shreeram S, Sparks A, Lane DP, Blow JJ (2002) Cell type-specific responses of human cells to inhibition of replication licensing. Oncogene 21(43):6624–6632. https://doi.org/10.1038/sj.onc.1205910

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  126. Siddiqui K, On KF, Diffley JF (2013) Regulating DNA replication in eukarya. Cold Spring Harb Perspect Biol 5(9). https://doi.org/10.1101/cshperspect.a012930

  127. Sir JH, Barr AR, Nicholas AK, Carvalho OP, Khurshid M, Sossick A, Reichelt S, D’Santos C, Woods CG, Gergely F (2011) A primary microcephaly protein complex forms a ring around parental centrioles. Nat Genet 43(11):1147–1153. https://doi.org/10.1038/ng.971

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  128. Sluder G (2013) Centriole engagement: it’s not just cohesin any more. Curr Biol 23(15):R659–R660. https://doi.org/10.1016/j.cub.2013.06.064

    CAS  PubMed  Article  Google Scholar 

  129. Song R, Walentek P, Sponer N, Klimke A, Lee JS, Dixon G, Harland R, Wan Y, Lishko P, Lize M, Kessel M, He L (2014) miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110. Nature 510(7503):115–120. https://doi.org/10.1038/nature13413

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  130. Spassky N, Meunier A (2017) The development and functions of multiciliated epithelia. Nat Rev Mol Cell Biol

  131. Spella M, Britz O, Kotantaki P, Lygerou Z, Nishitani H, Ramsay RG, Flordellis C, Guillemot F, Mantamadiotis T, Taraviras S (2007) Licensing regulators Geminin and Cdt1 identify progenitor cells of the mouse CNS in a specific phase of the cell cycle. Neuroscience 147(2):373–387. https://doi.org/10.1016/j.neuroscience.2007.03.050

    CAS  PubMed  Article  Google Scholar 

  132. Spella M, Kyrousi C, Kritikou E, Stathopoulou A, Guillemot F, Kioussis D, Pachnis V, Lygerou Z, Taraviras S (2011) Geminin regulates cortical progenitor proliferation and differentiation. Stem Cells 29(8):1269–1282. https://doi.org/10.1002/stem.678

    CAS  PubMed  Article  Google Scholar 

  133. Stathopoulou A, Natarajan D, Nikolopoulou P, Patmanidi AL, Lygerou Z, Pachnis V, Taraviras S (2016) Inactivation of geminin in neural crest cells affects the generation and maintenance of enteric progenitor cells, leading to enteric aganglionosis. Dev Biol 409(2):392–405. https://doi.org/10.1016/j.ydbio.2015.11.023

    CAS  PubMed  Article  Google Scholar 

  134. Stiff T, Alagoz M, Alcantara D, Outwin E, Brunner HG, Bongers EMHF, O’Driscoll M, Jeggo PA (2013) Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of Meier-Gorlin syndrome. PLoS Genet 9(3):e1003360. https://doi.org/10.1371/journal.pgen.1003360

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  135. Strnad P, Gonczy P (2008) Mechanisms of procentriole formation. Trends Cell Biol 18(8):389–396. https://doi.org/10.1016/j.tcb.2008.06.004

    CAS  PubMed  Article  Google Scholar 

  136. Strnad P, Leidel S, Vinogradova T, Euteneuer U, Khodjakov A, Gonczy P (2007) Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle. Dev Cell 13(2):203–213. https://doi.org/10.1016/j.devcel.2007.07.004

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  137. Stubbs JL, Oishi I, Izpisua Belmonte JC, Kintner C (2008) The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos. Nat Genet 40(12):1454–1460. https://doi.org/10.1038/ng.267

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  138. Stubbs JL, Vladar EK, Axelrod JD, Kintner C (2012) Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation. Nat Cell Biol 14(2):140–147. https://doi.org/10.1038/ncb2406

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  139. Symeonidou IE, Taraviras S, Lygerou Z (2012) Control over DNA replication in time and space. FEBS Lett 586(18):2803–2812. https://doi.org/10.1016/j.febslet.2012.07.042

    CAS  PubMed  Article  Google Scholar 

  140. Tachibana KE, Gonzalez MA, Guarguaglini G, Nigg EA, Laskey RA (2005) Depletion of licensing inhibitor geminin causes centrosome overduplication and mitotic defects. EMBO Rep 6(11):1052–1057. https://doi.org/10.1038/sj.embor.7400527

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  141. Tachibana KE, Nigg EA (2006) Geminin regulates multiple steps of the chromosome inheritance cycle. Cell Cycle 5(2):151–154. https://doi.org/10.4161/cc.5.2.2363

    CAS  PubMed  Article  Google Scholar 

  142. Tada S, Li A, Maiorano D, Mechali M, Blow JJ (2001) Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nat Cell Biol 3(2):107–113. https://doi.org/10.1038/35055000

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  143. Tadokoro T, Wang Y, Barak LS, Bai Y, Randell SH, Hogan BL (2014) IL-6/STAT3 promotes regeneration of airway ciliated cells from basal stem cells. Proc Natl Acad Sci U S A 111(35):E3641–E3649. https://doi.org/10.1073/pnas.1409781111

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  144. Tan FE, Vladar EK, Ma L, Fuentealba LC, Hoh R, Espinoza FH, Axelrod JD, Alvarez-Buylla A, Stearns T, Kintner C, Krasnow MA (2013) Myb promotes centriole amplification and later steps of the multiciliogenesis program. Development 140(20):4277–4286. https://doi.org/10.1242/dev.094102

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  145. Tang CJ, Lin SY, Hsu WB et al (2011) The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation. EMBO J 30(23):4790–4804. https://doi.org/10.1038/emboj.2011.378

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  146. Tang TK (2013) Centriole biogenesis in multiciliated cells. Nat Cell Biol 15(12):1400–1402. https://doi.org/10.1038/ncb2892

    CAS  PubMed  Article  Google Scholar 

  147. Terre B, Piergiovanni G, Segura-Bayona S et al (2016) GEMC1 is a critical regulator of multiciliated cell differentiation. EMBO J 35(9):942–960. 10.15252/embj.201592821

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  148. Thepaut M, Maiorano D, Guichou JF, Auge MT, Dumas C, Mechali M, Padilla A (2004) Crystal structure of the coiled-coil dimerization motif of geminin: structural and functional insights on DNA replication regulation. J Mol Biol 342(1):275–287. https://doi.org/10.1016/j.jmb.2004.06.065

    CAS  PubMed  Article  Google Scholar 

  149. Tsao PN, Vasconcelos M, Izvolsky KI, Qian J, Lu J, Cardoso WV (2009) Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development 136(13):2297–2307. https://doi.org/10.1242/dev.034884

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  150. Tsou MF, Stearns T (2006) Mechanism limiting centrosome duplication to once per cell cycle. Nature 442(7105):947–951. https://doi.org/10.1038/nature04985

    CAS  PubMed  Article  Google Scholar 

  151. Tsou MF, Wang WJ, George KA, Uryu K, Stearns T, Jallepalli PV (2009) Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells. Dev Cell 17(3):344–354. https://doi.org/10.1016/j.devcel.2009.07.015

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  152. Ullah Z, Lee CY, Lilly MA, DePamphilis ML (2009) Developmentally programmed endoreduplication in animals. Cell Cycle 8(10):1501–1509. https://doi.org/10.4161/cc.8.10.8325

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  153. Vetro A, Savasta S, Russo Raucci A, Cerqua C, Sartori G, Limongelli I, Forlino A, Maruelli S, Perucca P, Vergani D, Mazzini G, Mattevi A, Stivala LA, Salviati L, Zuffardi O (2017) MCM5: a new actor in the link between DNA replication and Meier-Gorlin syndrome. Eur J Hum Genet 25(5):646–650. https://doi.org/10.1038/ejhg.2017.5

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  154. Villa M, Crotta S, Dingwell KS, Hirst EMA, Gialitakis M, Ahlfors H, Smith JC, Stockinger B, Wack A (2016) The aryl hydrocarbon receptor controls cyclin O to promote epithelial multiciliogenesis. Nat Commun 7:12652. https://doi.org/10.1038/ncomms12652

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  155. Vladar EK, Mitchell BJ (2016) It’s a family act: the geminin triplets take center stage in motile ciliogenesis. EMBO J 35(9):904–906. 10.15252/embj.201694206

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  156. Vladar EK, Stearns T (2007) Molecular characterization of centriole assembly in ciliated epithelial cells. J Cell Biol 178(1):31–42. https://doi.org/10.1083/jcb.200703064

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  157. Vulprecht J, David A, Tibelius A, Castiel A, Konotop G, Liu F, Bestvater F, Raab MS, Zentgraf H, Izraeli S, Kramer A (2012) STIL is required for centriole duplication in human cells. J Cell Sci 125(5):1353–1362. https://doi.org/10.1242/jcs.104109

    CAS  PubMed  Article  Google Scholar 

  158. Walentek P, Quigley IK, Sun DI, Sajjan UK, Kintner C, Harland RM (2016) Ciliary transcription factors and miRNAs precisely regulate Cp110 levels required for ciliary adhesions and ciliogenesis. elife 5. https://doi.org/10.7554/eLife.17557

  159. Wallmeier J, Al-Mutairi DA, Chen CT, Loges NT, Pennekamp P, Menchen T, Ma L, Shamseldin HE, Olbrich H, Dougherty GW, Werner C, Alsabah BH, Köhler G, Jaspers M, Boon M, Griese M, Schmitt-Grohé S, Zimmermann T, Koerner-Rettberg C, Horak E, Kintner C, Alkuraya FS, Omran H (2014) Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia. Nat Genet 46(6):646–651. https://doi.org/10.1038/ng.2961

    CAS  PubMed  Article  Google Scholar 

  160. Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A (2000) Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science 290(5500):2309–2312. https://doi.org/10.1126/science.290.5500.2309

    CAS  PubMed  Article  Google Scholar 

  161. Wohlschlegel JA, Kutok JL, Weng AP, Dutta A (2002) Expression of geminin as a marker of cell proliferation in normal tissues and malignancies. Am J Pathol 161(1):267–273. https://doi.org/10.1016/S0002-9440(10)64178-8

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  162. Xouri G, Lygerou Z, Nishitani H, Pachnis V, Nurse P, Taraviras S (2004) Cdt1 and geminin are down-regulated upon cell cycle exit and are over-expressed in cancer-derived cell lines. Eur J Biochem 271(16):3368–3378. https://doi.org/10.1111/j.1432-1033.2004.04271.x

    CAS  PubMed  Article  Google Scholar 

  163. Xouri G, Squire A, Dimaki M, Geverts B, Verveer PJ, Taraviras S, Nishitani H, Houtsmuller AB, Bastiaens PIH, Lygerou Z (2007) Cdt1 associates dynamically with chromatin throughout G1 and recruits Geminin onto chromatin. EMBO J 26(5):1303–1314. https://doi.org/10.1038/sj.emboj.7601597

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  164. Xu X, Huang S, Zhang B, Huang F, Chi W, Fu J, Wang G, Li S, Jiang Q, Zhang C (2017) DNA replication licensing factor Cdc6 and Plk4 kinase antagonistically regulate centrosome duplication via Sas-6. Nat Commun 8:15164. https://doi.org/10.1038/ncomms15164

    PubMed  PubMed Central  Article  Google Scholar 

  165. Yellajoshyula D, Lim JW, Thompson DM Jr, Witt JS, Patterson ES, Kroll KL (2012) Geminin regulates the transcriptional and epigenetic status of neuronal fate-promoting genes during mammalian neurogenesis. Mol Cell Biol 32(22):4549–4560. https://doi.org/10.1128/MCB.00737-12

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  166. Yoshida K, Inoue I (2004) Regulation of Geminin and Cdt1 expression by E2F transcription factors. Oncogene 23(21):3802–3812. https://doi.org/10.1038/sj.onc.1207488

    CAS  PubMed  Article  Google Scholar 

  167. Yu X, Ng CP, Habacher H, Roy S (2008) Foxj1 transcription factors are master regulators of the motile ciliogenic program. Nat Genet 40(12):1445–1453. https://doi.org/10.1038/ng.263

    CAS  PubMed  Article  Google Scholar 

  168. Zegerman P (2015) Evolutionary conservation of the CDK targets in eukaryotic DNA replication initiation. Chromosoma 124(3):309–321. https://doi.org/10.1007/s00412-014-0500-y

    PubMed  Article  Google Scholar 

  169. Zhao H, Zhu L, Zhu Y, Cao J, Li S, Huang Q, Xu T, Huang X, Yan X, Zhu X (2013) The Cep63 paralogue Deup1 enables massive de novo centriole biogenesis for vertebrate multiciliogenesis. Nat Cell Biol 15(12):1434–1444. https://doi.org/10.1038/ncb2880

    CAS  PubMed  Article  Google Scholar 

  170. Zhou F, Narasimhan V, Shboul M, Chong YL, Reversade B, Roy S (2015) Gmnc is a master regulator of the multiciliated cell differentiation program. Curr Biol 25(24):3267–3273. https://doi.org/10.1016/j.cub.2015.10.062

    CAS  PubMed  Article  Google Scholar 

  171. Zhu W, Chen Y, Dutta A (2004) Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint. Mol Cell Biol 24(16):7140–7150. https://doi.org/10.1128/MCB.24.16.7140-7150.2004

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  172. Zielke N, Edgar BA, DePamphilis ML (2013) Endoreplication. Cold Spring Harb Perspect Biol 5(1):a012948. https://doi.org/10.1101/cshperspect.a012948

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  173. Zitouni S, Francia ME, Leal F, Montenegro Gouveia S, Nabais C, Duarte P, Gilberto S, Brito D, Moyer T, Kandels-Lewis S, Ohta M, Kitagawa D, Holland AJ, Karsenti E, Lorca T, Lince-Faria M, Bettencourt-Dias M (2016) CDK1 prevents unscheduled PLK4-STIL complex assembly in centriole biogenesis. Curr Biol 26(9):1127–1137. https://doi.org/10.1016/j.cub.2016.03.055

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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Acknowledgements

We thank the members of our laboratories for input and discussions and M. Verras for professional assistance with figure design.

Funding

Our work is supported by the European Research Council (ERC-StG 281851 and ERC-PoC 755284) and Fondation Sante.

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Correspondence to Zoi Lygerou.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Arbi, M., Pefani, D., Taraviras, S. et al. Controlling centriole numbers: Geminin family members as master regulators of centriole amplification and multiciliogenesis. Chromosoma 127, 151–174 (2018). https://doi.org/10.1007/s00412-017-0652-7

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Keywords

  • Geminin
  • GMNN
  • GemC1
  • GMNC
  • Lynkeas
  • McIdas
  • Idas
  • Multicilin