{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:32:31Z","timestamp":1791088351120,"version":"4.1.0"},"reference-count":137,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009880","name":"Regione Lazio","doi-asserted-by":"publisher","award":["85-2017-15348"],"award-info":[{"award-number":["85-2017-15348"]}],"id":[{"id":"10.13039\/501100009880","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PRIN-MIUR","award":["2017FNZRN3_005"],"award-info":[{"award-number":["2017FNZRN3_005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Regulators of mitotic division, when dysfunctional or expressed in a deregulated manner (over- or underexpressed) in somatic cells, cause chromosome instability, which is a predisposing condition to cancer that is associated with unrestricted proliferation. Genes encoding mitotic regulators are growingly implicated in neurodevelopmental diseases. Here, we briefly summarize existing knowledge on how microcephaly-related mitotic genes operate in the control of chromosome segregation during mitosis in somatic cells, with a special focus on the role of kinetochore factors. Then, we review evidence implicating mitotic apparatus- and kinetochore-resident factors in the origin of congenital microcephaly. We discuss data emerging from these works, which suggest a critical role of correct mitotic division in controlling neuronal cell proliferation and shaping the architecture of the central nervous system.<\/jats:p>","DOI":"10.3390\/cells9010049","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T10:28:43Z","timestamp":1577183323000},"page":"49","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The Mitotic Apparatus and Kinetochores in Microcephaly and Neurodevelopmental Diseases"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9312-0794","authenticated-orcid":false,"given":"Francesca","family":"Degrassi","sequence":"first","affiliation":[{"name":"IBPM Institute of Molecular Biology and Pathology, CNR Consiglio Nazionale delle Ricerche, c\/o Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Damizia","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3310-6701","authenticated-orcid":false,"given":"Patrizia","family":"Lavia","sequence":"additional","affiliation":[{"name":"IBPM Institute of Molecular Biology and Pathology, CNR Consiglio Nazionale delle Ricerche, c\/o Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1101\/gad.314351.118","article-title":"The impact of mitotic errors on cell proliferation and tumorigenesis","volume":"32","author":"Levine","year":"2018","journal-title":"Genes Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a029611","DOI":"10.1101\/cshperspect.a029611","article-title":"Chromosomal instability as a driver of tumor heterogeneity and evolution","volume":"7","author":"Bakhoum","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev-genom-083117-021441","article-title":"The Genetics of Primary Microcephaly","volume":"19","author":"Jayaraman","year":"2018","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/ng1449","article-title":"Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B","volume":"36","author":"Hanks","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1136\/jmedgenet-2014-102691","article-title":"The kinetochore protein, CENPF, is mutated in human ciliopathy and microcephaly phenotypes","volume":"52","author":"Waters","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/wdev.89","article-title":"Genetic causes of microcephaly and lessons for neuronal development","volume":"2","author":"Gilmore","year":"2013","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/j.1469-8749.1991.tb14813.x","article-title":"The predictive value of microcephaly during the first year of life for mental retardation at seven years","volume":"33","author":"Dolk","year":"1991","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.mcp.2015.05.015","article-title":"What next-generation sequencing (NGS) technology has enabled us to learn about primary autosomal recessive microcephaly (MCPH)","volume":"29","author":"Kaindl","year":"2015","journal-title":"Mol. Cell. Probes"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/ng.3311","article-title":"Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome","volume":"47","author":"Nguyen","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4836","DOI":"10.1093\/hmg\/ddx362","article-title":"Copb2 is essential for embryogenesis and hypomorphic mutations cause human microcephaly","volume":"26","author":"DiStasio","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kadir, R., Harel, T., Markus, B., Perez, Y., Bakhrat, A., Cohen, I., Volodarsky, M., Feintsein-Linial, M., Chervinski, E., and Zlotogora, J. (2016). ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1005919"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1083\/jcb.201510015","article-title":"Thirty years of search and capture: The complex simplicity of mitotic spindle assembly","volume":"211","author":"Heald","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1146\/annurev-biochem-060815-014528","article-title":"Mechanisms of Mitotic Spindle Assembly","volume":"85","author":"Petry","year":"2016","journal-title":"Annu. Rev. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nrm.2016.162","article-title":"Mitotic spindle assembly in animal cells: A fine balancing act","volume":"18","author":"Prosser","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/978-3-319-58592-5_18","article-title":"Molecular Mechanisms of Spindle Assembly Checkpoint Activation and Silencing","volume":"56","author":"Corbett","year":"2017","journal-title":"Prog. Mol. Subcell. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-cellbio-100616-060827","article-title":"Assessing the Contributions of Motor Enzymes and Microtubule Dynamics to Mitotic Chromosome Motions","volume":"33","author":"McIntosh","year":"2017","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1086\/341283","article-title":"Identification of microcephalin, a protein implicated in determining the size of the human brain","volume":"71","author":"Jackson","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1086\/422855","article-title":"Mutations in microcephalin cause aberrant regulation of chromosome condensation","volume":"75","author":"Trimborn","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15105","DOI":"10.1073\/pnas.0507722102","article-title":"BRIT1\/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly","volume":"102","author":"Lin","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.cell.2012.10.043","article-title":"Microcephaly gene links trithorax and REST\/NRSF to control neural stem cell proliferation and differentiation","volume":"151","author":"Yang","year":"2012","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1128\/MCB.17.4.2326","article-title":"Identification and characterization of interactions between the vertebrate polycomb-group protein BMI1 and human homologs of polyhomeotic","volume":"17","author":"Gunster","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1093\/hmg\/ddt072","article-title":"Mutation in PHC1 implicates chromatin remodeling in primary microcephaly pathogenesis","volume":"22","author":"Awad","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6996","DOI":"10.1128\/MCB.20.18.6996-7006.2000","article-title":"A Human Condensin Complex Containing hCAP-C-hCAP-E and CNAP1, a Homolog of Xenopus XCAP-D2, Colocalizes with Phosphorylated Histone H3 during the Early Stage of Mitotic Chromosome Condensation","volume":"20","author":"Schmiesing","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/417197a","article-title":"Cnd2 has dual roles in mitotic condensation and interphase","volume":"417","author":"Aono","year":"2002","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0092-8674(03)00724-4","article-title":"Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells","volume":"115","author":"Ono","year":"2003","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1101\/gad.286351.116","article-title":"Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis","volume":"30","author":"Martin","year":"2016","journal-title":"Genes Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1086\/302777","article-title":"A third novel locus for primary autosomal recessive microcephaly maps to chromosome 9q34","volume":"66","author":"Moynihan","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.1242\/jcs.020248","article-title":"Cep68 and Cep215 (Cdk5rap2) are required for centrosome cohesion","volume":"120","author":"Graser","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1242\/dev.040410","article-title":"Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors","volume":"137","author":"Lizarraga","year":"2010","journal-title":"Development"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nature09327","article-title":"Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations","volume":"467","author":"Louvi","year":"2010","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5409","DOI":"10.1007\/s12035-017-0778-x","article-title":"The Role of WD40-Repeat Protein 62 (MCPH2) in Brain Growth: Diverse Molecular and Cellular Mechanisms Required for Cortical Development","volume":"55","author":"Shohayeb","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.devcel.2007.07.002","article-title":"Plk4-Induced Centriole Biogenesis in Human Cells","volume":"13","author":"Westendorf","year":"2007","journal-title":"Dev. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.ajhg.2012.03.016","article-title":"A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function","volume":"90","author":"Hussain","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/nature02166","article-title":"Proteomic characterization of the human centrosome by protein correlation profiling","volume":"426","author":"Andersen","year":"2003","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ajhg.2010.06.003","article-title":"Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4","volume":"87","author":"Guernsey","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/ncb1220","article-title":"SAS-6 defines a protein family required for centrosome duplication in C. elegans and in human cells","volume":"7","author":"Leidel","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5940","DOI":"10.1093\/hmg\/ddu318","article-title":"A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous pakistani family","volume":"23","author":"Khan","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7813","DOI":"10.1128\/MCB.20.20.7813-7825.2000","article-title":"Protein 4.1 R-135 Interacts with a Novel Centrosomal Protein (CPAP) Which Is Associated with the gamma -Tubulin Complex","volume":"20","author":"Hung","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1136\/jmg.40.7.540","article-title":"A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13q12.2","volume":"40","author":"Leal","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/ng1539","article-title":"A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size","volume":"37","author":"Bond","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.ajhg.2009.01.017","article-title":"Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly","volume":"84","author":"Kumar","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1242\/jcs.104109","article-title":"STIL is required for centriole duplication in human cells","volume":"125","author":"Vulprecht","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ng995","article-title":"ASPM is a major determinant of cerebral cortical size","volume":"32","author":"Bond","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10438","DOI":"10.1073\/pnas.0604066103","article-title":"Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells","volume":"103","author":"Fish","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/humu.23381","article-title":"Autosomal recessive primary microcephaly due to ASPM mutations: An update","volume":"39","author":"Drunat","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"29706","DOI":"10.1074\/jbc.273.45.29706","article-title":"Citron Rho-interacting kinase, a novel tissue-specific Ser\/Thr kinase encompassing the Rho-Rac-binding protein citron","volume":"273","author":"Calautti","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ajhg.2016.07.004","article-title":"Biallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly","volume":"99","author":"Li","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1083\/jcb.200511061","article-title":"KIF14 and citron kinase act together to promote efficient cytokinesis","volume":"172","author":"Gruneberg","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/ana.25044","article-title":"Mutations of KIF14 cause primary microcephaly by impairing cytokinesis","volume":"82","author":"Moawia","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/brain\/awz004","article-title":"Mutations in the microtubule-associated protein MAP11 (C7orf43) cause microcephaly in humans and zebrafish","volume":"142","author":"Perez","year":"2019","journal-title":"Brain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5306","DOI":"10.1093\/hmg\/dds386","article-title":"Kinetochore KMN network gene CASC5 mutated in primary microcephaly","volume":"21","author":"Genin","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/359536a0","article-title":"CENP-E is a putative kinetochore motor that accumulates just before mitosis","volume":"359","author":"Yen","year":"1992","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s00439-014-1443-3","article-title":"Mutations in CENPE define a novel kinetochore-centromeric mechanism for microcephalic primordial dwarfism","volume":"133","author":"Mirzaa","year":"2014","journal-title":"Hum. Genet."},{"key":"ref_54","first-page":"2077","article-title":"Identification of G1 kinase activity for cdk6, a novel cyclin D partner","volume":"14","author":"Meyerson","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5199","DOI":"10.1093\/hmg\/ddt374","article-title":"CDK6 associates with the centrosome during mitosis and is mutated in a large pakistani family with primary microcephaly","volume":"22","author":"Hussain","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.cell.2012.04.043","article-title":"Coordination of kinase and phosphatase activities by Lem4 enables nuclear envelope reassembly during mitosis","volume":"150","author":"Asencio","year":"2012","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41436-018-0140-3","article-title":"Genomic and phenotypic delineation of congenital microcephaly","volume":"21","author":"Shaheen","year":"2019","journal-title":"Genet. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"330","DOI":"10.4161\/auto.6.3.11226","article-title":"p62\/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies\/ALIS and their degradation by autophagy","volume":"6","author":"Clausen","year":"2010","journal-title":"Autophagy"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1002\/j.1460-2075.1993.tb05946.x","article-title":"A 102 kDa subunit of a Golgi-associated particle has homology to beta subunits of trimeric G proteins","volume":"12","author":"Lewis","year":"1993","journal-title":"EMBO J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/BJ20080165","article-title":"Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis","volume":"416","author":"Angers","year":"2008","journal-title":"Biochem. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/ncb2746","article-title":"Centrosome amplification causes microcephaly","volume":"15","author":"Marthiens","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-3-319-57127-0_2","article-title":"Consequences of centrosome dysfunction during brain development","volume":"Volume 1002","author":"Nano","year":"2017","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/ncb2958","article-title":"Mitotic spindle multipolarity without centrosome amplification","volume":"16","author":"Maiato","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1093\/cercor\/bhu285","article-title":"Ranbp1, Deleted in DiGeorge\/22q11.2 Deletion Syndrome, is a Microcephaly Gene That Selectively Disrupts Layer 2\/3 Cortical Projection Neuron Generation","volume":"25","author":"Paronett","year":"2015","journal-title":"Cereb. Cortex"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1242\/jcs.00624","article-title":"Mammalian RanBP1 regulates centrosome cohesion during mitosis","volume":"116","author":"Ciciarello","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10577-015-9514-4","article-title":"The GTPase RAN regulates multiple steps of the centrosome life cycle","volume":"24","author":"Lavia","year":"2016","journal-title":"Chromosome Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"dev170613","DOI":"10.1242\/dev.170613","article-title":"A centrosomal view of CNS growth","volume":"145","author":"Saade","year":"2018","journal-title":"Development"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1007\/s00439-016-1724-0","article-title":"CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly","volume":"135","author":"Basit","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.ajhg.2016.07.003","article-title":"Mutations in Citron Kinase Cause Recessive Microlissencephaly with Multinucleated Neurons","volume":"99","author":"Harding","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1007\/s00439-016-1722-2","article-title":"Mutations in CIT, encoding citron rho-interacting serine\/threonine kinase, cause severe primary microcephaly in humans","volume":"135","author":"Shaheen","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1016\/j.celrep.2017.01.054","article-title":"Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly","volume":"18","author":"Bianchi","year":"2017","journal-title":"Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.15252\/embr.201745023","article-title":"ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules","volume":"18","author":"Gai","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Bianchi, F.T., Gai, M., Berto, G.E., and Di Cunto, F. (2017). Of rings and spines: The multiple facets of Citron proteins in neural development. Small GTPases, 1\u20139.","DOI":"10.1080\/21541248.2017.1374325"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1242\/jcs.200253","article-title":"Citron kinase\u2014Renaissance of a neglected mitotic kinase","volume":"130","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.neuron.2019.03.009","article-title":"Dissecting the Toxic Effects of Zika Virus Proteins on Neural Progenitor Cells","volume":"101","author":"Ferreira","year":"2019","journal-title":"Neuron"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/ajmg.a.31069","article-title":"MonoallelicBUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome","volume":"140A","author":"Matsuura","year":"2006","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-3-319-57127-0_4","article-title":"Kinetochore malfunction in human pathologies","volume":"Volume 1002","author":"Kops","year":"2017","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.ccell.2018.03.007","article-title":"Genomic and Functional Approaches to Understanding Cancer Aneuploidy","volume":"33","author":"Taylor","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ceb.2018.02.005","article-title":"Kinetochore assembly and disassembly during mitotic entry and exit","volume":"52","author":"Hara","year":"2018","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"jcs231985","DOI":"10.1242\/jcs.231985","article-title":"Force-generating mechanisms of anaphase in human cells","volume":"132","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.tcb.2005.06.008","article-title":"Aneuploidy: A matter of bad connections","volume":"15","author":"Cimini","year":"2005","journal-title":"Trends Cell Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.tcb.2011.01.003","article-title":"Merotelic kinetochore attachment: Causes and effects","volume":"21","author":"Gregan","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrm2163","article-title":"The spindle-assembly checkpoint in space and time","volume":"8","author":"Musacchio","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ceb.2016.02.016","article-title":"Attachment issues: Kinetochore transformations and spindle checkpoint silencing","volume":"39","author":"Etemad","year":"2016","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrm3494","article-title":"Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore","volume":"14","author":"Foley","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"R1002","DOI":"10.1016\/j.cub.2015.08.051","article-title":"The Molecular Biology of Spindle Assembly Checkpoint Signaling Dynamics","volume":"25","author":"Musacchio","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/ncb1576","article-title":"The outer plate in vertebrate kinetochores is a flexible network with multiple microtubule interactions","volume":"9","author":"Dong","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.tcb.2010.10.007","article-title":"Sensing centromere tension: Aurora B and the regulation of kinetochore function","volume":"21","author":"Lampson","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1083\/jcb.200208092","article-title":"The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint","volume":"161","author":"Hauf","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/nrm.2015.5","article-title":"The molecular basis for centromere identity and function","volume":"17","author":"McKinley","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.sbi.2016.03.003","article-title":"Progress in the structural and functional characterization of kinetochores","volume":"37","author":"Pesenti","year":"2016","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3389\/fcell.2018.00062","article-title":"Kinase and phosphatase cross-talk at the kinetochore","volume":"6","author":"Saurin","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1086\/302640","article-title":"Primary autosomal recessive microcephaly: Homozygosity mapping of MCPH4 to chromosome 15","volume":"65","author":"Jamieson","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s10048-015-0468-7","article-title":"Refining the phenotype associated with CASC5 mutation","volume":"17","author":"Saadi","year":"2016","journal-title":"Neurogenetics"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00439-015-1619-5","article-title":"A novel homozygous splicing mutation of CASC5 causes primary microcephaly in a large Pakistani family","volume":"135","author":"Szczepanski","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1002\/ajmg.a.37726","article-title":"First clinical report of an infant with microcephaly and CASC5 mutations","volume":"170","author":"Zarate","year":"2016","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00412-013-0446-5","article-title":"KNL1: Bringing order to the kinetochore","volume":"123","author":"Caldas","year":"2014","journal-title":"Chromosoma"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1038\/s41467-019-10411-w","article-title":"Robust elimination of genome-damaged cells safeguards against brain somatic aneuploidy following Knl1 deletion","volume":"10","author":"Shi","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1126\/science.1210214","article-title":"Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations","volume":"333","author":"Janssen","year":"2011","journal-title":"Science"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature10802","article-title":"DNA breaks and chromosome pulverization from errors in mitosis","volume":"482","author":"Crasta","year":"2012","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.devcel.2017.05.022","article-title":"Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System","volume":"41","author":"Santaguida","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.celrep.2018.09.032","article-title":"Microcephaly Modeling of Kinetochore Mutation Reveals a Brain-Specific Phenotype","volume":"25","author":"Li","year":"2018","journal-title":"Cell Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.1158\/0008-5472.CAN-09-4319","article-title":"Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidy","volume":"70","author":"Suijkerbuijk","year":"2010","journal-title":"Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e05269","DOI":"10.7554\/eLife.05269","article-title":"A molecular basis for the differential roles of Bubl and BubR1 in the spindle assembly checkpoint","volume":"4","author":"Overlack","year":"2015","journal-title":"eLife"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"10084","DOI":"10.1074\/jbc.RA118.003154","article-title":"The kinetochore proteins CENP-E and CENP-F directly and specifically interact with distinct BUB mitotic checkpoint Ser\/Thr kinases","volume":"293","author":"Ciossani","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/s41422-019-0178-z","article-title":"BubR1 phosphorylates CENP-E as a switch enabling the transition from lateral association to end-on capture of spindle microtubules","volume":"29","author":"Huang","year":"2019","journal-title":"Cell Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.devcel.2012.09.005","article-title":"Integration of Kinase and Phosphatase Activities by BUBR1 Ensures Formation of Stable Kinetochore-Microtubule Attachments","volume":"23","author":"Suijkerbuijk","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1093\/hmg\/ddz022","article-title":"Nearly complete deletion of BubR1 causes microcephaly through shortened mitosis and massive cell death","volume":"28","author":"Simmons","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/ng.822","article-title":"Mutations in CEP57 cause mosaic variegated aneuploidy syndrome","volume":"43","author":"Snape","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"10151","DOI":"10.1038\/ncomms10151","article-title":"Cep57 is a Mis12-interacting kinetochore protein involved in kinetochore targeting of Mad1-Mad2","volume":"7","author":"Zhou","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1038\/ng.3883","article-title":"Biallelic TRIP13 mutations predispose to Wilms tumor and chromosome missegregation","volume":"49","author":"Yost","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/35019518","article-title":"CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint","volume":"2","author":"Yao","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1083\/jcb.200303167","article-title":"Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss","volume":"162","author":"Weaver","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1083\/jcb.201202152","article-title":"CENP-E--dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint","volume":"198","author":"Guo","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1080\/15384101.2019.1617615","article-title":"A tension-independent mechanism reduces Aurora B-mediated phosphorylation upon microtubule capture by CENP-E at the kinetochore","volume":"18","author":"Taveras","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ccr.2006.12.003","article-title":"Aneuploidy Acts Both Oncogenically and as a Tumor Suppressor","volume":"11","author":"Weaver","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s00412-005-0046-0","article-title":"Cenp-F (mitosin) is more than a mitotic marker","volume":"115","author":"Varis","year":"2006","journal-title":"Chromosoma"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1083\/jcb.130.3.507","article-title":"CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis","volume":"130","author":"Liao","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"19545","DOI":"10.1074\/jbc.270.33.19545","article-title":"The C terminus of mitosin is essential for its nuclear localization, centromere\/kinetochore targeting, and dimerization","volume":"270","author":"Zhu","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1242\/jcs.062075","article-title":"Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F","volume":"123","author":"Gurden","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1007\/s00412-006-0049-5","article-title":"CENP-F is a novel microtubule-binding protein that is essential for kinetochore attachments and affects the duration of the mitotic checkpoint delay","volume":"115","author":"Feng","year":"2006","journal-title":"Chromosoma"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/sj.cr.7290172","article-title":"Mitosin\/CENP-F is a conserved kinetochore protein subjected to cytoplasmic dynein-mediated poleward transport","volume":"13","author":"Yang","year":"2003","journal-title":"Cell Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.cub.2007.05.077","article-title":"Cenp-F Links Kinetochores to Ndel1\/Nde1\/Lis1\/Dynein Microtubule Motor Complexes","volume":"17","author":"Vergnolle","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1083\/jcb.201007118","article-title":"A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase","volume":"192","author":"Bolhy","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1080\/15384101.2018.1520569","article-title":"Regulation of Cenp-F localization to nuclear pores and kinetochores","volume":"17","author":"Berto","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1038\/sj.emboj.7601642","article-title":"The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions","volume":"26","author":"Zuccolo","year":"2007","journal-title":"EMBO J."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/humu.22960","article-title":"Str\u00f8mme Syndrome Is a Ciliary Disorder Caused by Mutations in CENPF","volume":"37","author":"Filges","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/ajmg.a.38173","article-title":"A further family of Stromme syndrome carrying CENPF mutation","volume":"173","author":"Ozkinay","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1083\/jcb.200108007","article-title":"Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export","volume":"155","author":"Vasu","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.cell.2013.08.024","article-title":"XDynein recruitment to nuclear pores activates apical nuclear migration and mitotic entry in brain progenitor cells","volume":"154","author":"Hu","year":"2013","journal-title":"Cell"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Splinter, D., Tanenbaum, M.E., Lindqvist, A., Jaarsma, D., Flotho, A., Yu, K.L., Grigoriev, I., Engelsma, D., Haasdijk, E.D., and Keijzer, N. (2010). Bicaudal D2, Dynein, and Kinesin-1 Associate with Nuclear Pore Complexes and Regulate Centrosome and Nuclear Positioning during Mitotic Entry. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000350"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1002\/ana.25370","article-title":"Homozygous splicing mutation in NUP133 causes Galloway-Mowat syndrome","volume":"84","author":"Fujita","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1136\/jmedgenet-2016-104237","article-title":"Homozygous mutation in NUP107 leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway-Mowat syndrome","volume":"54","author":"Rosti","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"8894","DOI":"10.1038\/ncomms9894","article-title":"Aneuploidy causes premature differentiation of neural and intestinal stem cells","volume":"6","author":"Gogendeau","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1083\/jcb.201607022","article-title":"Centrosome and spindle assembly checkpoint loss leads to neural apoptosis and reduced brain size","volume":"216","author":"Poulton","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ceb.2017.11.010","article-title":"Present and future of modeling human brain development in 3D organoids","volume":"49","author":"Quadrato","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.molmed.2018.09.005","article-title":"Brain Organoids and the Study of Neurodevelopment","volume":"24","author":"Trujillo","year":"2018","journal-title":"Trends Mol. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/1\/49\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:45:14Z","timestamp":1760190314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/1\/49"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,24]]},"references-count":137,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["cells9010049"],"URL":"https:\/\/doi.org\/10.3390\/cells9010049","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,24]]}}}