Skip to main content
SpringerLink
Log in

The Janus soul of centrosomes: a paradoxical role in disease?

  • Review
  • Published:
Chromosome Research Aims and scope Submit manuscript

Abstract

The centrosome is the main microtubule organizing center of animal cells. It contributes to spindle assembly and orientation during mitosis and to ciliogenesis in interphase. Numerical and structural defects in this organelle are known to be associated with developmental disorders such as dwarfism and microcephaly, but only recently, the molecular mechanisms linking centrosome aberrations to altered physiology are being elucidated. Defects in centrosome number or structure have also been described in cancer. These opposite clinical outcomes—arising from reduced proliferation and overproliferation respectively—can be explained in light of the tissue- and developmental-specific requirements for centrosome functions. The pathological outcomes of centrosome deficiencies have become clearer when considering its consequences. Among them, there are genetic instability (mainly aneuploidy, a defect in chromosome number), defects in the symmetry of cell division (important for cell fate specification and tissue architecture) and impaired ciliogenesis. In this review, we discuss the origins and the consequences of centrosome flaws, with particular attention on how they contribute to developmental diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

Ana2:

Anastral spindle 2

ASPM:

Abnormal spindle-like microcephaly-associated protein

BRCA1:

Breast cancer type 1 susceptibility protein

Bub3:

Budding uninhibited by benzimidazoles 3

BubR1:

Budding uninhibited by benzimidazoles related kinase 1

Cnn:

Centrosomin

CDK6:

Cyclin-dependent kinase 6

CDK5RAP2:

CDK5 regulatory subunit associated protein 2

CEP63:

Centrosomal protein of 63 kDa

CEP135:

Centrosomal protein of 135 kDa

CEP152:

Centrosomal protein of 152 kDa

CPAP:

Centrobin-centrosomal protein associated protein

Dm:

Drosophila melanogaster

Mad2:

Mitotic arrest deficient 2

MT:

Microtubule

MTOC:

Microtubule organizing center

NSC:

Neural stem cell

PCNT:

Pericentrin

PCD:

Primary cilia dyskinesia

PCM:

Pericentriolar material

Plk-4:

Polo-like kinase 4

MCPH:

Autosomal recessive primary microcephaly

MOPD-II:

Microcephalic osteodysplastic primordial dwarfism type II

SAC:

Spindle assembly checkpoint

SAS-4:

Spindle assembly abnormal protein 4

SAS-6:

Spindle assembly abnormal protein 6

SCKS:

Seckel syndrome spindle assembly checkpoint

Shh:

Sonic hedgehog Seckel syndrome

STIL:

SCL/TAL1 interrupting locus sonic hedgehog

TUBGCP4:

Gamma-tubulin complex component 4

WDR62:

WD repeat-containing protein 62

References

  • Afzelius BA (1976) A human syndrome caused by immotile cilia. Science 193:317–319

    Article  CAS  PubMed  Google Scholar 

  • 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 516:104–107

    CAS  PubMed  Google Scholar 

  • Al-Dosari MS, Shaheen R, Colak D, Alkuraya FS (2010) Novel CENPJ mutation causes Seckel syndrome. J Med Genet 47:411–414

    Article  CAS  PubMed  Google Scholar 

  • Anderson RG (1972) The three-dimensional structure of the basal body from the rhesus monkey oviduct. J Cell Biol 54:246–265

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Anderson CT, Stearns T (2009) Centriole age underlies asynchronous primary cilium growth in mammalian cells. Curr Biol 19:1498–1502

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Arquint C, Nigg EA (2014) STIL microcephaly mutations interfere with APC/C-mediated degradation and cause centriole amplification. Curr Biol 24:351–360

    Article  CAS  PubMed  Google Scholar 

  • Avidor-Reiss T, Maer AM, Koundakjian E, Polyanovsky A, Keil T, Subramaniam S, Zuker CS (2004) Decoding cilia function: defining specialized genes required for compartmentalized cilia biogenesis. Cell 117:527–539

    Article  CAS  PubMed  Google Scholar 

  • Azimzadeh J, Wong ML, Downhour DM, Sanchez Alvarado A, Marshall WF (2012) Centrosome loss in the evolution of planarians. Science 335:461–463

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Babu JR, Jeganathan KB, Baker DJ, Wu X, Kang-Decker N, van Deursen JM (2003) Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation. J Cell Biol 160:341–353

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Badano JL, Mitsuma N, Beales PL, Katsanis N (2006) The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet 7:125–148

    Article  CAS  PubMed  Google Scholar 

  • Baker DJ, Jeganathan KB, Cameron JD, Thompson M, Juneja S, Kopecka A, Kumar R, Jenkins RB, de Groen PC, Roche P et al (2004) BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat Genet 36:744–749

    Article  CAS  PubMed  Google Scholar 

  • Baker DJ, Dawlaty MM, Wijshake T, Jeganathan KB, Malureanu L, van Ree JH, Crespo-Diaz R, Reyes S, Seaburg L, Shapiro V et al (2013) Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. Nat Cell Biol 15:96–102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Barrera JA, Kao LR, Hammer RE, Seemann J, Fuchs JL, Megraw TL (2010) CDK5RAP2 regulates centriole engagement and cohesion in mice. Dev Cell 18:913–926

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Basto R, Lau J, Vinogradova T, Gardiol A, Woods CG, Khodjakov A, Raff JW (2006) Flies without centrioles. Cell 125:1375–1386

    Article  CAS  PubMed  Google Scholar 

  • Basto R, Brunk K, Vinadogrova T, Peel N, Franz A, Khodjakov A, Raff JW (2008) Centrosome amplification can initiate tumorigenesis in flies. Cell 133:1032–1042

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bate M, Martinez-Arias A (1993) The development of drosophila melanogaster. Cold Spring Harbor Laboratory Press

  • Bazzi H, Anderson KV (2014) Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo. Proc Natl Acad Sci U S A 111:E1491–E1500

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bettencourt-Dias M, Rodrigues-Martins A, Carpenter L, Riparbelli M, Lehmann L, Gatt MK, Carmo N, Balloux F, Callaini G, Glover DM (2005) SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol 15:2199–2207

    Article  CAS  PubMed  Google Scholar 

  • Bettencourt-Dias M, Hildebrandt F, Pellman D, Woods G, Godinho SA (2011) Centrosomes and cilia in human disease. Trends Genet 27:307–315

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Blachon S, Gopalakrishnan J, Omori Y, Polyanovsky A, Church A, Nicastro D, Malicki J, Avidor-Reiss T (2008) Drosophila asterless and vertebrate Cep152 are orthologs essential for centriole duplication. Genetics 180:2081–2094

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bond J, Roberts E, Springell K, Lizarraga SB, Scott S, Higgins J, Hampshire DJ, Morrison EE, Leal GF, Silva EO et al (2005) A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet 37:353–355

    Article  CAS  PubMed  Google Scholar 

  • Boveri T (2008) Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. J Cell Sci 121(Suppl 1):1–84

    Article  PubMed  Google Scholar 

  • Brinkley BR, Cox SM, Pepper DA, Wible L, Brenner SL, Pardue RL (1981) Tubulin assembly sites and the organization of cytoplasmic microtubules in cultured mammalian cells. J Cell Biol 90:554–562

    Article  CAS  PubMed  Google Scholar 

  • Calarco-Gillam PD, Siebert MC, Hubble R, Mitchison T, Kirschner M (1983) Centrosome development in early mouse embryos as defined by an autoantibody against pericentriolar material. Cell 35:621–629

    Article  CAS  PubMed  Google Scholar 

  • Cardona A, Hartenstein V, Romero R (2006) Early embryogenesis of planaria: a cryptic larva feeding on maternal resources. Dev Genes Evol 216:667–681

    Article  PubMed  Google Scholar 

  • Carvalho-Santos Z, Azimzadeh J, Pereira-Leal JB, Bettencourt-Dias M (2011) Evolution: tracing the origins of centrioles, cilia, and flagella. J Cell Biol 194:165–175

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Castellanos E, Dominguez P, Gonzalez C (2008) Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr Biol 18:1209–1214

    Article  CAS  PubMed  Google Scholar 

  • Caussinus E, Gonzalez C (2005) Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet 37:1125–1129

    Article  CAS  PubMed  Google Scholar 

  • Chan JY (2011) A clinical overview of centrosome amplification in human cancers. Int J Biol Sci 7:1122–1144

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chang MY, Ong AC (2008) Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and treatment. Nephron Physiol 108:1–7

    Article  CAS  Google Scholar 

  • Chavali PL, Putz M, Gergely F (2014) Small organelle, big responsibility: the role of centrosomes in development and disease. Philos Trans R Soc Lond B Biol Sci 369

  • Clarke PR, Zhang C (2008) Spatial and temporal coordination of mitosis by Ran GTPase. Nat Rev Mol Cell Biol 9:464–477

    Article  CAS  PubMed  Google Scholar 

  • Clement CA, Kristensen SG, Mollgard K, Pazour GJ, Yoder BK, Larsen LA, Christensen ST (2009) The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation. J Cell Sci 122:3070–3082

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Connolly JA, Kiosses BW, Kalnins VI (1986) Centrioles are lost as embryonic myoblasts fuse into myotubes in vitro. Eur J Cell Biol 39:341–345

    CAS  PubMed  Google Scholar 

  • Cuschieri A, Bannister LH (1975) The development of the olfactory mucosa in the mouse: electron microscopy. J Anat 119:471–498

    PubMed Central  CAS  PubMed  Google Scholar 

  • D’Assoro AB, Lingle WL, Salisbury JL (2002) Centrosome amplification and the development of cancer. Oncogene 21:6146–6153

    Article  PubMed  CAS  Google Scholar 

  • David A, Liu F, Tibelius A, Vulprecht J, Wald D, Rothermel U, Ohana R, Seitel A, Metzger J, Ashery-Padan R et al (2014) Lack of centrioles and primary cilia in STIL−/− mouse embryos. Cell Cycle 13:2859–2868

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • De Mey J, Lambert AM, Bajer AS, Moeremans M, De Brabander M (1982) Visualization of microtubules in interphase and mitotic plant cells of Haemanthus endosperm with the immuno-gold staining method. Proc Natl Acad Sci U S A 79:1898–1902

    Article  PubMed Central  PubMed  Google Scholar 

  • Deng W, Lin H (1997) Spectrosomes and fusomes anchor mitotic spindles during asymmetric germ cell divisions and facilitate the formation of a polarized microtubule array for oocyte specification in Drosophila. Dev Biol 189:79–94

    Article  CAS  PubMed  Google Scholar 

  • Dinarina A, Pugieux C, Corral MM, Loose M, Spatz J, Karsenti E, Nedelec F (2009) Chromatin shapes the mitotic spindle. Cell 138:502–513

    Article  CAS  PubMed  Google Scholar 

  • Dirksen ER (1971) Centriole morphogenesis in developing ciliated epithelium of the mouse oviduct. J Cell Biol 51:286–302

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dobles M, Liberal V, Scott ML, Benezra R, Sorger PK (2000) Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2. Cell 101:635–645

    Article  CAS  PubMed  Google Scholar 

  • Duncan AW, Taylor MH, Hickey RD, Hanlon Newell AE, Lenzi ML, Olson SB, Finegold MJ, Grompe M (2010) The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature 467:707–710

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Faggioli F, Vezzoni P, Montagna C (2011) Single-cell analysis of ploidy and centrosomes underscores the peculiarity of normal hepatocytes. PLoS One 6, e26080

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

  • Firat-Karalar EN, Rauniyar N, Yates JR 3rd, Stearns T (2014) Proximity interactions among centrosome components identify regulators of centriole duplication. Curr Biol 24:664–670

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fish JL, Dehay C, Kennedy H, Huttner WB (2008) Making bigger brains-the evolution of neural-progenitor-cell division. J Cell Sci 121:2783–2793

    Article  CAS  PubMed  Google Scholar 

  • Fliegauf M, Benzing T, Omran H (2007) When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol 8:880–893

    Article  CAS  PubMed  Google Scholar 

  • Frasch M, Glover DM, Saumweber H (1986) Nuclear antigens follow different pathways into daughter nuclei during mitosis in early Drosophila embryos. J Cell Sci 82:155–172

    CAS  PubMed  Google Scholar 

  • Fujimori A, Itoh K, Goto S, Hirakawa H, Wang B, Kokubo T, Kito S, Tsukamoto S, Fushiki S (2014) Disruption of Aspm causes microcephaly with abnormal neuronal differentiation. Brain Dev 36:661–669

    Article  PubMed  Google Scholar 

  • Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT, Pellman D (2005) Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 437:1043–1047

    Article  CAS  PubMed  Google Scholar 

  • Fukasawa K (2005) Centrosome amplification, chromosome instability and cancer development. Cancer Lett 230:6–19

    Article  CAS  PubMed  Google Scholar 

  • Ganem NJ, Storchova Z, Pellman D (2007) Tetraploidy, aneuploidy and cancer. Curr Opin Genet Dev 17:157–162

    Article  CAS  PubMed  Google Scholar 

  • Ganem NJ, Godinho SA, Pellman D (2009) A mechanism linking extra centrosomes to chromosomal instability. Nature 460:278–282

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Giansanti MG, Gatti M, Bonaccorsi S (2001) The role of centrosomes and astral microtubules during asymmetric division of Drosophila neuroblasts. Development 128:1137–1145

    CAS  PubMed  Google Scholar 

  • Glover DM, Leibowitz MH, McLean DA, Parry H (1995) Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 81:95–105

    Article  CAS  PubMed  Google Scholar 

  • Godinho SA, Pellman D (2014) Causes and consequences of centrosome abnormalities in cancer. Philos Trans R Soc Lond B Biol Sci 369

  • Godinho SA, Kwon M, Pellman D (2009) Centrosomes and cancer: how cancer cells divide with too many centrosomes. Cancer Metastasis Rev 28:85–98

    Article  CAS  PubMed  Google Scholar 

  • Godinho SA, Picone R, Burute M, Dagher R, Su Y, Leung CT, Polyak K, Brugge JS, Thery M, Pellman D (2014) Oncogene-like induction of cellular invasion from centrosome amplification. Nature 510:167–171

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Goetz SC, Anderson KV (2010) The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 11:331–344

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gomes R, Karess RE, Ohkura H, Glover DM, Sunkel CE (1993) Abnormal anaphase resolution (aar): a locus required for progression through mitosis in Drosophila. J Cell Sci 104(Pt 2):583–593

    PubMed  Google Scholar 

  • Gonczy P (2012) Towards a molecular architecture of centriole assembly. Nat Rev Mol Cell Biol 13:425–435

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez C (2007) Spindle orientation, asymmetric division and tumour suppression in Drosophila stem cells. Nat Rev Genet 8:462–472

    Article  CAS  PubMed  Google Scholar 

  • Goshima G, Mayer M, Zhang N, Stuurman N, Vale RD (2008) Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle. J Cell Biol 181:421–429

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Graser S, Stierhof YD, Lavoie SB, Gassner OS, Lamla S, Le Clech M, Nigg EA (2007) Cep164, a novel centriole appendage protein required for primary cilium formation. J Cell Biol 179:321–330

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Griffith E, Walker S, Martin CA, Vagnarelli P, Stiff T, Vernay B, Al Sanna N, Saggar A, Hamel B, Earnshaw WC et al (2008) Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling. Nat Genet 40:232–236

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guernsey DL, Jiang H, Hussin J, Arnold M, Bouyakdan K, Perry S, Babineau-Sturk T, Beis J, Dumas N, Evans SC et al (2010) Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4. Am J Hum Genet 87:40–51

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gueth-Hallonet C, Antony C, Aghion J, Santa-Maria A, Lajoie-Mazenc I, Wright M, Maro B (1993) gamma-Tubulin is present in acentriolar MTOCs during early mouse development. J Cell Sci 105(Pt 1):157–166

    CAS  PubMed  Google Scholar 

  • Guidotti JE, Bregerie O, Robert A, Debey P, Brechot C, Desdouets C (2003) Liver cell polyploidization: a pivotal role for binuclear hepatocytes. J Biol Chem 278:19095–19101

    Article  CAS  PubMed  Google Scholar 

  • Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA (2005) The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol 7:1140–1146

    Article  CAS  PubMed  Google Scholar 

  • Hardy PA, Zacharias H (2005) Reappraisal of the Hansemann-Boveri hypothesis on the origin of tumors. Cell Biol Int 29:983–992

    Article  PubMed  Google Scholar 

  • Hayward D, Metz J, Pellacani C, Wakefield JG (2014) Synergy between multiple microtubule-generating pathways confers robustness to centrosome-driven mitotic spindle formation. Dev Cell 28:81–93

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Heald R, Tournebize R, Blank T, Sandaltzopoulos R, Becker P, Hyman A, Karsenti E (1996) Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382:420–425

    Article  CAS  PubMed  Google Scholar 

  • Hildebrandt F, Benzing T, Katsanis N (2011) Ciliopathies. N Engl J Med 364:1533–1543

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hinchcliffe EH, Miller FJ, Cham M, Khodjakov A, Sluder G (2001) Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291:1547–1550

    Article  CAS  PubMed  Google Scholar 

  • 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 26:2684–2689

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Holubcova Z, Blayney M, Elder K, Schuh M (2015) Human oocytes. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes. Science 348:1143–1147

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV (2003) Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426:83–87

    Article  CAS  PubMed  Google Scholar 

  • Hudson JW, Kozarova A, Cheung P, Macmillan JC, Swallow CJ, Cross JC, Dennis JW (2001) Late mitotic failure in mice lacking Sak, a polo-like kinase. Curr Biol 11:441–446

    Article  CAS  PubMed  Google Scholar 

  • Hussain MS, Baig SM, Neumann S, Peche VS, Szczepanski S, Nurnberg G, Tariq M, Jameel M, Khan TN, Fatima A et al (2013) CDK6 associates with the centrosome during mitosis and is mutated in a large Pakistani family with primary microcephaly. Hum Mol Genet 22:5199–5214

    Article  CAS  PubMed  Google Scholar 

  • Ibanez-Tallon I, Pagenstecher A, Fliegauf M, Olbrich H, Kispert A, Ketelsen UP, North A, Heintz N, Omran H (2004) Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation. Hum Mol Genet 13:2133–2141

    Article  CAS  PubMed  Google Scholar 

  • Insolera R, Bazzi H, Shao W, Anderson KV, Shi SH (2014) Cortical neurogenesis in the absence of centrioles. Nat Neurosci 17:1528–1535

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ishikawa H, Marshall WF (2011) Ciliogenesis: building the cell’s antenna. Nat Rev Mol Cell Biol 12:222–234

    Article  CAS  PubMed  Google Scholar 

  • Izraeli S, Lowe LA, Bertness VL, Good DJ, Dorward DW, Kirsch IR, Kuehn MR (1999) The SIL gene is required for mouse embryonic axial development and left-right specification. Nature 399:691–694

    Article  CAS  PubMed  Google Scholar 

  • Jackson AP, McHale DP, Campbell DA, Jafri H, Rashid Y, Mannan J, Karbani G, Corry P, Levene MI, Mueller RF et al (1998) Primary autosomal recessive microcephaly (MCPH1) maps to chromosome 8p22-pter. Am J Hum Genet 63:541–546

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tuysuz B, Nurnberg G et al (2011) CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet 43:23–26

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Khan MA, Rupp VM, Orpinell M, Hussain MS, Altmuller J, Steinmetz MO, Enzinger C, Thiele H, Hohne W, Nurnberg G et al (2014) A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family. Hum Mol Genet 23:5940–5949

    Article  PubMed  Google Scholar 

  • Khodjakov A, Cole RW, Oakley BR, Rieder CL (2000) Centrosome-independent mitotic spindle formation in vertebrates. Curr Biol 10:59–67

    Article  CAS  PubMed  Google Scholar 

  • Khodjakov A, Rieder CL, Sluder G, Cassels G, Sibon O, Wang CL (2002) De novo formation of centrosomes in vertebrate cells arrested during S phase. J Cell Biol 158:1171–1181

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Khodjakov A, Copenagle L, Gordon MB, Compton DA, Kapoor TM (2003) Minus-end capture of preformed kinetochore fibers contributes to spindle morphogenesis. J Cell Biol 160:671–683

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA (2007) Plk4-induced centriole biogenesis in human cells. Dev Cell 13:190–202

    Article  CAS  PubMed  Google Scholar 

  • Klos Dehring DA, Vladar EK, Werner ME, Mitchell JW, Hwang P, Mitchell BJ (2013) Deuterosome-mediated centriole biogenesis. Dev Cell 27:103–112

    Article  CAS  PubMed  Google Scholar 

  • Knoblich JA (2010) Asymmetric cell division: recent developments and their implications for tumour biology. Nat Rev Mol Cell Biol 11:849–860

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ko MA, Rosario CO, Hudson JW, Kulkarni S, Pollett A, Dennis JW, Swallow CJ (2005) Plk4 haploinsufficiency causes mitotic infidelity and carcinogenesis. Nat Genet 37:883–888

    Article  CAS  PubMed  Google Scholar 

  • Kramer A, Maier B, Bartek J (2011) Centrosome clustering and chromosomal (in) stability: a matter of life and death. Mol Oncol 5:324–335

    Article  PubMed  CAS  Google Scholar 

  • 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 84:286–290

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kushner EJ, Ferro LS, Liu JY, Durrant JR, Rogers SL, Dudley AC, Bautch VL (2014) Excess centrosomes disrupt endothelial cell migration via centrosome scattering. J Cell Biol 206:257–272

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kwon M, Godinho SA, Chandhok NS, Ganem NJ, Azioune A, Thery M, Pellman D (2008) Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev 22:2189–2203

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lambrus BG, Uetake Y, Clutario KM, Daggubati V, Snyder M, Sluder G, Holland AJ (2015) p53 protects against genome instability following centriole duplication failure. J Cell Biol 210:63–77

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA (2013) Cerebral organoids model human brain development and microcephaly. Nature 501:373–379

    Article  CAS  PubMed  Google Scholar 

  • Leber B, Maier B, Fuchs F, Chi J, Riffel P, Anderhub S, Wagner L, Ho AD, Salisbury JL, Boutros M et al (2010) Proteins required for centrosome clustering in cancer cells. Sci Transl Med 2:33ra38

    Article  PubMed  CAS  Google Scholar 

  • Lizarraga SB, Margossian SP, Harris MH, Campagna DR, Han AP, Blevins S, Mudbhary R, Barker JE, Walsh CA, Fleming MD (2010) Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors. Development 137:1907–1917

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lopes CS, Sampaio P, Williams B, Goldberg M, Sunkel CE (2005) The Drosophila Bub3 protein is required for the mitotic checkpoint and for normal accumulation of cyclins during G2 and early stages of mitosis. J Cell Sci 118:187–198

    Article  CAS  PubMed  Google Scholar 

  • Mahjoub MR (2013) The importance of a single primary cilium. Organogenesis 9:61–69

    Article  PubMed Central  PubMed  Google Scholar 

  • Mahjoub MR, Stearns T (2012) Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling. Curr Biol 22:1628–1634

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Maiato H, Rieder CL, Khodjakov A (2004) Kinetochore-driven formation of kinetochore fibers contributes to spindle assembly during animal mitosis. J Cell Biol 167:831–840

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Manandhar G, Schatten H, Sutovsky P (2005) Centrosome reduction during gametogenesis and its significance. Biol Reprod 72:2–13

    Article  CAS  PubMed  Google Scholar 

  • Marjanovic M, Sanchez-Huertas C, Terre B, Gomez R, Scheel JF, Pacheco S, Knobel PA, Martinez-Marchal A, Aivio S, Palenzuela L et al (2015) CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination. Nat Commun 6:7676

    Article  PubMed Central  PubMed  Google Scholar 

  • Marthiens V, Piel M, Basto R (2012) Never tear us apart—the importance of centrosome clustering. J Cell Sci 125:3281–3292

    Article  CAS  PubMed  Google Scholar 

  • Marthiens V, Rujano MA, Pennetier C, Tessier S, Paul-Gilloteaux P, Basto R (2013) Centrosome amplification causes microcephaly. Nat Cell Biol 15:731–740

    Article  CAS  PubMed  Google Scholar 

  • Martin CA, Ahmad I, Klingseisen A, Hussain MS, Bicknell LS, Leitch A, Nurnberg G, Toliat MR, Murray JE, Hunt D et al (2014) Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat Genet 46:1283–1292

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Megraw TL, Kao LR, Kaufman TC (2001) Zygotic development without functional mitotic centrosomes. Curr Biol 11:116–120

    Article  CAS  PubMed  Google Scholar 

  • Meraldi P, Honda R, Nigg EA (2002) Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53−/− cells. EMBO J 21:483–492

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Michel LS, Liberal V, Chatterjee A, Kirchwegger R, Pasche B, Gerald W, Dobles M, Sorger PK, Murty VV, Benezra R (2001) MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 409:355–359

    Article  CAS  PubMed  Google Scholar 

  • Mora-Bermudez F, Matsuzaki F, Huttner WB (2014) Specific polar subpopulations of astral microtubules control spindle orientation and symmetric neural stem cell division. Elife 3

  • Morin X, Bellaiche Y (2011) Mitotic spindle orientation in asymmetric and symmetric cell divisions during animal development. Dev Cell 21:102–119

    Article  CAS  PubMed  Google Scholar 

  • Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8:379–393

    Article  CAS  PubMed  Google Scholar 

  • Nagaoka SI, Hodges CA, Albertini DF, Hunt PA (2011) Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors. Curr Biol 21:651–657

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nakajima Y, Meyer EJ, Kroesen A, McKinney SA, Gibson MC (2013) Epithelial junctions maintain tissue architecture by directing planar spindle orientation. Nature 500:359–362

    Article  CAS  PubMed  Google Scholar 

  • Nezi L, Musacchio A (2009) Sister chromatid tension and the spindle assembly checkpoint. Curr Opin Cell Biol 21:785–795

    Article  CAS  PubMed  Google Scholar 

  • Nicholas AK, Khurshid M, Desir J, Carvalho OP, Cox JJ, Thornton G, Kausar R, Ansar M, Ahmad W, Verloes A et al (2010) WDR62 is associated with the spindle pole and is mutated in human microcephaly. Nat Genet 42:1010–1014

    Article  CAS  PubMed  Google Scholar 

  • Nigg EA, Raff JW (2009) Centrioles, centrosomes, and cilia in health and disease. Cell 139:663–678

    Article  CAS  PubMed  Google Scholar 

  • Noatynska A, Gotta M, Meraldi P (2012) Mitotic spindle (DIS)orientation and DISease: cause or consequence? J Cell Biol 199:1025–1035

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nonaka S, Tanaka Y, Okada Y, Takeda S, Harada A, Kanai Y, Kido M, Hirokawa N (1998) Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95:829–837

    Article  CAS  PubMed  Google Scholar 

  • Paridaen JT, Wilsch-Brauninger M, Huttner WB (2013) Asymmetric inheritance of centrosome-associated primary cilium membrane directs ciliogenesis after cell division. Cell 155:333–344

    Article  CAS  PubMed  Google Scholar 

  • Parker JD, Hilton LK, Diener DR, Rasi MQ, Mahjoub MR, Rosenbaum JL, Quarmby LM (2010) Centrioles are freed from cilia by severing prior to mitosis. Cytoskeleton (Hoboken) 67:425–430

    Article  Google Scholar 

  • Pattison L, Crow YJ, Deeble VJ, Jackson AP, Jafri H, Rashid Y, Roberts E, Woods CG (2000) A fifth locus for primary autosomal recessive microcephaly maps to chromosome 1q31. Am J Hum Genet 67:1578–1580

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Peel N, Stevens NR, Basto R, Raff JW (2007) Overexpressing centriole-replication proteins in vivo induces centriole overduplication and de novo formation. Curr Biol 17:834–843

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Perez-Mongiovi D, Malmanche N, Bousbaa H, Sunkel C (2005) Maternal expression of the checkpoint protein BubR1 is required for synchrony of syncytial nuclear divisions and polar body arrest in Drosophila melanogaster. Development 132:4509–4520

    Article  CAS  PubMed  Google Scholar 

  • Pihan GA, Purohit A, Wallace J, Knecht H, Woda B, Quesenberry P, Doxsey SJ (1998) Centrosome defects and genetic instability in malignant tumors. Cancer Res 58:3974–3985

    CAS  PubMed  Google Scholar 

  • Poulton JS, Cuningham JC, Peifer M (2014) Acentrosomal Drosophila epithelial cells exhibit abnormal cell division, leading to cell death and compensatory proliferation. Dev Cell 30:731–745

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Quintyne NJ, Reing JE, Hoffelder DR, Gollin SM, Saunders WS (2005) Spindle multipolarity is prevented by centrosomal clustering. Science 307:127–129

    Article  CAS  PubMed  Google Scholar 

  • Rauch A, Thiel CT, Schindler D, Wick U, Crow YJ, Ekici AB, van Essen AJ, Goecke TO, Al-Gazali L, Chrzanowska KH et al (2008) Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science 319:816–819

    Article  CAS  PubMed  Google Scholar 

  • Rebollo E, Gonzalez C (2000) Visualizing the spindle checkpoint in Drosophila spermatocytes. EMBO Rep 1:65–70

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Richens JH, Barros TP, Lucas EP, Peel N, Pinto DM, Wainman A, Raff JW (2015) The Drosophila Pericentrin-like-protein (PLP) cooperates with Cnn to maintain the integrity of the outer PCM. Biol Open 4:1052–1061

    Article  PubMed Central  PubMed  Google Scholar 

  • Ricke RM, van Deursen JM (2013) Aneuploidy in health, disease, and aging. J Cell Biol 201:11–21

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rieder CL, Cole RW, Khodjakov A, Sluder G (1995) The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. J Cell Biol 130:941–948

    Article  CAS  PubMed  Google Scholar 

  • Ring D, Hubble R, Kirschner M (1982) Mitosis in a cell with multiple centrioles. J Cell Biol 94:549–556

    Article  CAS  PubMed  Google Scholar 

  • Riparbelli MG, Callaini G (2011) Male gametogenesis without centrioles. Dev Biol 349:427–439

    Article  CAS  PubMed  Google Scholar 

  • Roberts E, Hampshire DJ, Pattison L, Springell K, Jafri H, Corry P, Mannon J, Rashid Y, Crow Y, Bond J et al (2002) Autosomal recessive primary microcephaly: an analysis of locus heterogeneity and phenotypic variation. J Med Genet 39:718–721

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rodrigues-Martins A, Riparbelli M, Callaini G, Glover DM, Bettencourt-Dias M (2007) Revisiting the role of the mother centriole in centriole biogenesis. Science 316:1046–1050

    Article  CAS  PubMed  Google Scholar 

  • Rujano MA, Sanchez-Pulido L, Pennetier C, le Dez G, Basto R (2013) The microcephaly protein Asp regulates neuroepithelium morphogenesis by controlling the spatial distribution of myosin II. Nat Cell Biol 15:1294–1306

    Article  CAS  PubMed  Google Scholar 

  • Sabino D, Gogendeau D, Gambarotto D, Nano M, Pennetier C, Dingli F, Arras G, Loew D, Basto R (2015) Moesin is a major regulator of centrosome behavior in epithelial cells with extra centrosomes. Curr Biol 25:879–889

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sanderson MJ, Sleigh MA (1981) Ciliary activity of cultured rabbit tracheal epithelium: beat pattern and metachrony. J Cell Sci 47:331–347

    CAS  PubMed  Google Scholar 

  • Scaerou F, Aguilera I, Saunders R, Kane N, Blottiere L, Karess R (1999) The rough deal protein is a new kinetochore component required for accurate chromosome segregation in Drosophila. J Cell Sci 112(Pt 21):3757–3768

    CAS  PubMed  Google Scholar 

  • Schatten G (1994) The centrosome and its mode of inheritance: the reduction of the centrosome during gametogenesis and its restoration during fertilization. Dev Biol 165:299–335

    Article  CAS  PubMed  Google Scholar 

  • Scheidecker S, Etard C, Haren L, Stoetzel C, Hull S, Arno G, Plagnol V, Drunat S, Passemard S, Toutain A et al (2015) Mutations in TUBGCP4 alter microtubule organization via the gamma-tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy. Am J Hum Genet 96:666–674

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schoenfelder KP, Montague RA, Paramore SV, Lennox AL, Mahowald AP, Fox DT (2014) Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum. Development 141:3551–3560

    Article  CAS  PubMed  Google Scholar 

  • Shaheen R, Al Tala S, Almoisheer A, Alkuraya FS (2014) Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism. J Med Genet 51:814–816

    Article  PubMed  Google Scholar 

  • Shekhar MP, Lyakhovich A, Visscher DW, Heng H, Kondrat N (2002) Rad6 overexpression induces multinucleation, centrosome amplification, abnormal mitosis, aneuploidy, and transformation. Cancer Res 62:2115–2124

    CAS  PubMed  Google Scholar 

  • Silk AD, Zasadil LM, Holland AJ, Vitre B, Cleveland DW, Weaver BA (2013) Chromosome missegregation rate predicts whether aneuploidy will promote or suppress tumors. Proc Natl Acad Sci U S A 110:E4134–E4141

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Silkworth WT, Nardi IK, Scholl LM, Cimini D (2009) Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells. PLoS One 4, e6564

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Kronig C, Schermer B, Benzing T, Cabello OA, Jenny A et al (2005) Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet 37:537–543

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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 43:1147–1153

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sir JH, Putz M, Daly O, Morrison CG, Dunning M, Kilmartin JV, Gergely F (2013) Loss of centrioles causes chromosomal instability in vertebrate somatic cells. J Cell Biol 203:747–756

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sotillo R, Hernando E, Diaz-Rodriguez E, Teruya-Feldstein J, Cordon-Cardo C, Lowe SW, Benezra R (2007) Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell 11:9–23

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Srsen V, Fant X, Heald R, Rabouille C, Merdes A (2009) Centrosome proteins form an insoluble perinuclear matrix during muscle cell differentiation. BMC Cell Biol 10:28

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Stevens NR, Raposo AA, Basto R, St Johnston D, Raff JW (2007) From stem cell to embryo without centrioles. Curr Biol 17:1498–1503

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stiff T, Alagoz M, Alcantara D, Outwin E, Brunner HG, Bongers EM, 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, e1003360

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stinchcombe JC, Majorovits E, Bossi G, Fuller S, Griffiths GM (2006) Centrosome polarization delivers secretory granules to the immunological synapse. Nature 443:462–465

    Article  CAS  PubMed  Google Scholar 

  • Sunkel CE, Glover DM (1988) polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J Cell Sci 89(Pt 1):25–38

    PubMed  Google Scholar 

  • Szollosi D, Calarco P, Donahue RP (1972) Absence of centrioles in the first and second meiotic spindles of mouse oocytes. J Cell Sci 11:521–541

    CAS  PubMed  Google Scholar 

  • Tanos BE, Yang HJ, Soni R, Wang WJ, Macaluso FP, Asara JM, Tsou MF (2013) Centriole distal appendages promote membrane docking, leading to cilia initiation. Genes Dev 27:163–168

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tassin AM, Maro B, Bornens M (1985) Fate of microtubule-organizing centers during myogenesis in vitro. J Cell Biol 100:35–46

    Article  CAS  PubMed  Google Scholar 

  • Telley IA, Gaspar I, Ephrussi A, Surrey T (2012) Aster migration determines the length scale of nuclear separation in the Drosophila syncytial embryo. J Cell Biol 197:887–895

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tsou MF, Stearns T (2006) Mechanism limiting centrosome duplication to once per cell cycle. Nature 442:947–951

    Article  CAS  PubMed  Google Scholar 

  • 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 17:344–354

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vorobjev IA, Chentsov Yu S (1982) Centrioles in the cell cycle. I. Epithelial cells. J Cell Biol 93:938–949

    Article  CAS  PubMed  Google Scholar 

  • Wallingford JB, Mitchell B (2011) Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. Genes Dev 25:201–213

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wallmeier J, Al-Mutairi DA, Chen CT, Loges NT, Pennekamp P, Menchen T, Ma L, Shamseldin HE, Olbrich H, Dougherty GW et al (2014) Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia. Nat Genet 46:646–651

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Wu T, Kirschner MW (2014) The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium. Elife 3, e03083

    PubMed Central  PubMed  Google Scholar 

  • Waters AM, Beales PL (2011) Ciliopathies: an expanding disease spectrum. Pediatr Nephrol 26:1039–1056

    Article  PubMed Central  PubMed  Google Scholar 

  • Weaver BA, Cleveland DW (2006) Does aneuploidy cause cancer? Curr Opin Cell Biol 18:658–667

    Article  CAS  PubMed  Google Scholar 

  • Weaver BA, Silk AD, Montagna C, Verdier-Pinard P, Cleveland DW (2007) Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell 11:25–36

    Article  CAS  PubMed  Google Scholar 

  • Webber WA, Lee J (1975) Fine structure of mammalian renal cilia. Anat Rec 182:339–343

    Article  CAS  PubMed  Google Scholar 

  • Whitfield WG, Millar SE, Saumweber H, Frasch M, Glover DM (1988) Cloning of a gene encoding an antigen associated with the centrosome in Drosophila. J Cell Sci 89(Pt 4):467–480

    CAS  PubMed  Google Scholar 

  • Willaredt MA, Gorgas K, Gardner HA, Tucker KL (2012) Multiple essential roles for primary cilia in heart development. Cilia 1:23

    Article  PubMed Central  PubMed  Google Scholar 

  • Wong C, Stearns T (2005) Mammalian cells lack checkpoints for tetraploidy, aberrant centrosome number, and cytokinesis failure. BMC Cell Biol 6:6

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wong YL, Anzola JV, Davis RL, Yoon M, Motamedi A, Kroll A, Seo CP, Hsia JE, Kim SK, Mitchell JW et al (2015) Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4. Science 348:1155–1160

    Article  CAS  PubMed  Google Scholar 

  • Worthington WC Jr, Cathcart RS 3rd (1963) Ependymal cilia: distribution and activity in the adult human brain. Science 139:221–222

    Article  PubMed  Google Scholar 

  • Yamashita YM, Fuller MT (2005) Asymmetric stem cell division and function of the niche in the Drosophila male germ line. Int J Hematol 82:377–380

    Article  CAS  PubMed  Google Scholar 

  • Yamashita YM, Jones DL, Fuller MT (2003) Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301:1547–1550

    Article  CAS  PubMed  Google Scholar 

  • Zyss D, Gergely F (2009) Centrosome function in cancer: guilty or innocent? Trends Cell Biol 19:334–346

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank D. Gambarotto, D. Gogendeau and V. Marthiens for helpful comments on the manuscript. Work in our lab is supported by ERC starting grant (Centrostemcancer 242598), Institut Curie, CNRS, an FRM installation grant, ATIP grant and La Ligue contre le Cancer (M.N.). Our lab is a member of the CelTisPhyBio labex.

Author information

Authors and Affiliations

  1. Institut Curie, PSL Research University, CNRS UMR144, 12 rue Lhomond, 75005, Paris, France

    Maddalena Nano & Renata Basto

Authors
  1. Maddalena Nano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Renata Basto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Renata Basto.

Additional information

Responsible Editors: Daniela Cimini and Giulia Guarguaglini

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nano, M., Basto, R. The Janus soul of centrosomes: a paradoxical role in disease?. Chromosome Res 24, 127–144 (2016). https://doi.org/10.1007/s10577-015-9507-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10577-015-9507-3

Keywords

Search

Navigation