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Centrosome amplification (the formation of excess centrosomes) has been noted in renal cells of patients and animal models of various types of cystic kidney disease. Whether this defect plays a causal role in cystogenesis remains unknown. Here, we investigate the consequences of centrosome amplification during kidney development, homeostasis, and after injury. Increasing centrosome number in vivo perturbed proliferation and differentiation of renal progenitors, resulting in defective branching morphogenesis and renal hypoplasia. Centrosome amplification disrupted mitotic spindle morphology, ciliary assembly, and signaling pathways essential for the function of renal progenitors, highlighting the mechanisms underlying the developmental defects. Importantly, centrosome amplification was sufficient to induce rapid cystogenesis shortly after birth. Finally, we discovered that centrosome amplification sensitized kidneys in adult mice, causing cystogenesis after ischemic renal injury. Our study defines a new mechanism underlying the pathogenesis of renal cystogenesis, and identifies a potentially new cellular target for therapy.<\/jats:p>","DOI":"10.1083\/jcb.201710019","type":"journal-article","created":{"date-parts":[[2018,6,12]],"date-time":"2018-06-12T13:15:14Z","timestamp":1528809314000},"page":"2485-2501","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Centrosome amplification disrupts renal development and causes cystogenesis"],"prefix":"10.1083","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0403-7452","authenticated-orcid":true,"given":"Lai Kuan","family":"Dionne","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyuhwan","family":"Shim","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-1807","authenticated-orcid":false,"given":"Masato","family":"Hoshi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2771-8584","authenticated-orcid":true,"given":"Tao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Marthiens","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique\u2014Institute Curie, Paris, France 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Knoten","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5556-2770","authenticated-orcid":true,"given":"Renata","family":"Basto","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique\u2014Institute Curie, Paris, France 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2804-127X","authenticated-orcid":true,"given":"Sanjay","family":"Jain","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8129-7464","authenticated-orcid":true,"given":"Moe R.","family":"Mahjoub","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"},{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,6,12]]},"reference":[{"key":"2023072309500371800_bib1","doi-asserted-by":"publisher","first-page":"20130464","DOI":"10.1098\/rstb.2013.0464","article-title":"Centrosomes as signalling centres","volume":"369","author":"Arquint","year":"2014","journal-title":"Philos. 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