{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T19:59:17Z","timestamp":1784145557534,"version":"3.55.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004795","name":"Institut Universitaire de France","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Male gametogenesis involves both mitotic divisions to amplify germ cell progenitors that gradually differentiate and meiotic divisions. Centrosomal regulation is essential for both types of divisions, with centrioles remaining tightly paired during the interphase. Here, we generated and characterized the phenotype of mutant mice devoid of <jats:italic>Cep250\/C-Nap1<\/jats:italic>, a gene encoding for a docking protein for fibers linking centrioles, and characterized their phenotype. The <jats:italic>Cep250<\/jats:italic><jats:sup>-\/-<\/jats:sup> mice presented with no major defects, apart from male infertility due to a reduction in the spermatogonial pool and the meiotic blockade. Spermatogonial stem cells expressing Zbtb16 were not affected, whereas the differentiating spermatogonia were vastly lost. These cells displayed abnormal <jats:italic>\u03b3<\/jats:italic>H2AX-staining, accompanied by an increase in the apoptotic rate. The few germ cells that survived at this stage, entered the meiotic prophase I and were arrested at a pachytene-like stage, likely due to synapsis defects and the unrepaired DNA double-strand breaks. In these cells, centrosomes split up precociously, with <jats:italic>\u03b3<\/jats:italic>-tubulin foci being separated whereas these were closely associated in wild-type cells. Interestingly, this lack of cohesion was also observed in wild-type female meiocytes, likely explaining the normal fertility of <jats:italic>Cep250<\/jats:italic><jats:sup>-\/-<\/jats:sup> female mice. Taken together, this study proposes a specific requirement of centrosome cohesion in the male germline, with a crucial role of CEP250 in both differentiating spermatogonia and meiotic spermatocytes.<\/jats:p>","DOI":"10.3389\/fcell.2021.754054","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T17:30:46Z","timestamp":1642613446000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["CEP250 is Required for Maintaining Centrosome Cohesion in the Germline and Fertility in Male Mice"],"prefix":"10.3389","volume":"9","author":[{"given":"Sandrine","family":"Floriot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bellutti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Castille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Moison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Messiaen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Passet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Boulanger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhak","family":"Boukadiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Tourpin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beauvallet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marthe","family":"Vilotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Riviere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"P\u00e9choux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Bertaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Vilotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Livera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202051030","article-title":"PLK1 Regulates Centrosome Migration and Spindle Dynamics in Male Mouse Meiosis","volume":"22","author":"Alfaro","year":"2021","journal-title":"EMBO Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1242\/jcs.005231","article-title":"Structure and Duplication of the Centrosome","volume":"120","author":"Azimzadeh","year":"2007","journal-title":"J. Cel Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1083\/jcb.200504107","article-title":"Rootletin Forms Centriole-Associated Filaments and Functions in Centrosome Cohesion","volume":"171","author":"Bahe","year":"2005","journal-title":"J. Cel Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1038\/nrg3573","article-title":"Meiotic Recombination in Mammals: Localization and Regulation","volume":"14","author":"Baudat","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1002\/jcb.22517","article-title":"Characterization of Centrosomal Proteins Cep55 and Pericentrin in Intercellular Bridges of Mouse Testes","volume":"109","author":"Chang","year":"2010","journal-title":"J. Cel. Biochem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"7217","DOI":"10.1038\/ncomms8217","article-title":"A Three-step MTOC Fragmentation Mechanism Facilitates Bipolar Spindle Assembly in Mouse Oocytes","volume":"6","author":"Clift","year":"2015","journal-title":"Nat. Commun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.tcb.2012.02.007","article-title":"Acentrosomal Spindle Assembly and Chromosome Segregation during Oocyte Meiosis","volume":"22","author":"Dumont","year":"2012","journal-title":"Trends Cel Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"E2347","DOI":"10.1073\/pnas.1505683112","article-title":"Periodic Retinoic Acid-STRA8 Signaling Intersects with Periodic Germ-Cell Competencies to Regulate Spermatogenesis","volume":"112","author":"Endo","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B9","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1091\/mbc.E16-05-0325","article-title":"Centriole Splitting Caused by Loss of the Centrosomal Linker Protein C-NAP1 Reduces Centriolar Satellite Density and Impedes Centrosome Amplification","volume":"28","author":"Flanagan","year":"2017","journal-title":"MBoC"},{"key":"B10","doi-asserted-by":"publisher","first-page":"6894","DOI":"10.1038\/ncomms7894","article-title":"C-Nap1 Mutation Affects Centriole Cohesion and Is Associated with a Seckel-like Syndrome in Cattle","volume":"6","author":"Floriot","year":"2015","journal-title":"Nat. Commun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"a015800","DOI":"10.1101\/cshperspect.a015800","article-title":"The Centrosome and its Duplication Cycle","volume":"7","author":"Fu","year":"2015","journal-title":"Cold Spring Harb Perspect. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"17113","DOI":"10.1038\/s41598-018-35085-0","article-title":"High-throughput Sequencing for the Molecular Diagnosis of Usher Syndrome Reveals 42 Novel Mutations and Consolidates CEP250 as Usher-like Disease Causative","volume":"8","author":"Fuster-Garc\u00eda","year":"2018","journal-title":"Sci. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/physrev.00013.2015","article-title":"Spermatogenesis: The Commitment to Meiosis","volume":"96","author":"Griswold","year":"2016","journal-title":"Physiol. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1016\/j.celrep.2013.08.005","article-title":"LRRC45 Is a Centrosome Linker Component Required for Centrosome Cohesion","volume":"4","author":"He","year":"2013","journal-title":"Cel Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1007\/s43032-020-00354-9","article-title":"MicroRNA-449a Suppresses Mouse Spermatogonia Proliferation via Inhibition of CEP55","volume":"28","author":"Hua","year":"2021","journal-title":"Reprod. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1136\/jmedgenet-2014-102287","article-title":"A Homozygous Nonsense CEP250 Mutation Combined with a Heterozygous Nonsense C2orf71 Mutation Is Associated with Atypical Usher Syndrome","volume":"51","author":"Khateb","year":"2014","journal-title":"J. Med. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1080\/13816810.2018.1466338","article-title":"CEP250 Mutations Associated with Mild Cone-Rod Dystrophy and Sensorineural Hearing Loss in a Japanese Family","volume":"39","author":"Kubota","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1091\/MBC.E19-12-0701","article-title":"PLK1 Is Required for Chromosome Compaction and Microtubule Organization in Mouse Oocytes","volume":"31","author":"Little","year":"2020","journal-title":"MBoC"},{"key":"B38","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1002\/1529-0131(199803)41:3<551::AID-ART22>3.0.CO;2-X","article-title":"Autoantibodies to a Group of Centrosomal Proteins in Human Autoimmune Sera Reactive with the Centrosome","volume":"41","author":"Mack","year":"1998","journal-title":"Arthritis Rheum.."},{"key":"B19","doi-asserted-by":"publisher","first-page":"7676","DOI":"10.1038\/ncomms8676","article-title":"CEP63 Deficiency Promotes P53-dependent Microcephaly and Reveals a Role for the Centrosome in Meiotic Recombination","volume":"6","author":"Marjanovi\u0107","year":"2015","journal-title":"Nat. Commun."},{"key":"B20","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1083\/jcb.151.4.837","article-title":"The Centrosomal Protein C-Nap1 Is Required for Cell Cycle-Regulated Centrosome Cohesion","volume":"151","author":"Mayor","year":"2000","journal-title":"J. Cel Biol."},{"key":"B21","first-page":"111","article-title":"Method of Centrosome Isolation from Cultured Animal Cells","volume-title":"Cell Biology, a Laboratory Handbook","author":"Moudjou","year":"1998"},{"key":"B22","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s10577-015-9503-7","article-title":"Centrosomes in the DNA Damage Response-The Hub outside the centre","volume":"24","author":"Mullee","year":"2016","journal-title":"Chromosome Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e1005243","DOI":"10.1371\/journal.pgen.1005243","article-title":"The Centrosomal Linker and Microtubules Provide Dual Levels of Spatial Coordination of Centrosomes","volume":"11","author":"Panic","year":"2015","journal-title":"Plos Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3389\/fonc.2013.00277","article-title":"Centrosome Dysfunction Contributes to Chromosome Instability, Chromoanagenesis, and Genome Reprograming in Cancer","volume":"3","author":"Pihan","year":"2013","journal-title":"Front. Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"dev174128","DOI":"10.1242\/dev.174128","article-title":"WDR62 Is Involved in Spindle Assembly by Interacting with CEP170 in Spermatogenesis","volume":"146","author":"Qin","year":"2019","journal-title":"Dev"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/0471142727.mb1215s100","article-title":"Engineering Designer Transcription Activator\u2010\u2010Like Effector Nucleases (TALENs) by REAL or REAL\u2010Fast Assembly","volume":"100","author":"Reyon","year":"2012","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1269\/jrr.09039","article-title":"Emerging Connection between Centrosome and DNA Repair Machinery","volume":"50","author":"Shimada","year":"2009","journal-title":"Jrr"},{"key":"B28","doi-asserted-by":"publisher","first-page":"4984","DOI":"10.1096\/fj.201701096RR","article-title":"Cep55 Overexpression Causes Male\u2010specific Sterility in Mice by Suppressing Foxo1 Nuclear Retention through Sustained Activation of PI3K\/Akt Signaling","volume":"32","author":"Sinha","year":"2018","journal-title":"FASEB j."},{"key":"B29","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1101\/gad.1627708","article-title":"Cep164 Is a Mediator Protein Required for the Maintenance of Genomic Stability through Modulation of MDC1, RPA, and CHK1","volume":"22","author":"Sivasubramaniam","year":"2008","journal-title":"Genes Dev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/bs.ctdb.2019.01.011","article-title":"Sexually Dimorphic Germ Cell Identity in Mammals","volume":"134","author":"Spiller","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"4770","DOI":"10.1242\/jcs.104059","article-title":"The Centriolar Satellite Protein Cep131 Is Important for Genome Stability","volume":"125","author":"Staples","year":"2012","journal-title":"J. Cel Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/bs.ctdb.2016.11.013","article-title":"Roles of Retinoic Acid in Germ Cell Differentiation","volume":"125","author":"Teletin","year":"2017","journal-title":"Curr. Top. Dev. Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"E2246","DOI":"10.1073\/pnas.1716840115","article-title":"STED Nanoscopy of the Centrosome Linker Reveals a CEP68-Organized, Periodic Rootletin Network Anchored to a C-Nap1 Ring at Centrioles","volume":"115","author":"Vlijm","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e51023","DOI":"10.15252\/embr.202051023","article-title":"Overlapping Roles for PLK1 and Aurora A during Meiotic Centrosome Biogenesis in Mouse Spermatocytes","volume":"22","author":"Wellard","year":"2021","journal-title":"EMBO Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1091\/mbc.E05-10-0943","article-title":"Rootletin Interacts with C-Nap1 and May Function as a Physical Linker between the Pair of Centrioles\/basal Bodies in Cells","volume":"17","author":"Yang","year":"2006","journal-title":"MBoC"},{"key":"B36","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1002\/jcb.21195","article-title":"Centrosomal Localization of DNA Damage Checkpoint Proteins","volume":"101","author":"Zhang","year":"2007","journal-title":"J. Cel. Biochem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1095\/biolreprod.107.064337","article-title":"Expression of Stimulated by Retinoic Acid Gene 8 (Stra8) and Maturation of Murine Gonocytes and Spermatogonia Induced by Retinoic Acid In Vitro1","volume":"78","author":"Zhou","year":"2008","journal-title":"Biol. Reprod."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.754054\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T17:30:50Z","timestamp":1642613450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.754054\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,19]]},"references-count":38,"alternative-id":["10.3389\/fcell.2021.754054"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.754054","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,19]]},"article-number":"754054"}}