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Multiple processes coordinate spindle assembly and chromosome segregation. Two key components are centrosomes and the spindle assembly checkpoint (SAC), and mutations affecting either can cause human microcephaly. In vivo studies in Drosophila melanogaster found that loss of either component alone is well tolerated in the developing brain, in contrast to epithelial tissues of the imaginal discs. In this study, we reveal that one reason for that tolerance is the compensatory relationship between centrosomes and the SAC. In the absence of both centrosomes and the SAC, brain cells, including neural stem cells, experience massive errors in mitosis, leading to increased cell death, which reduces the neural progenitor pool and severely disrupts brain development. However, our data also demonstrate that neural cells are much more tolerant of aneuploidy than epithelial cells. Our data provide novel insights into the mechanisms by which different tissues manage genome stability and parallels with human microcephaly.<\/jats:p>","DOI":"10.1083\/jcb.201607022","type":"journal-article","created":{"date-parts":[[2017,3,29]],"date-time":"2017-03-29T14:11:27Z","timestamp":1490796687000},"page":"1255-1265","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Centrosome and spindle assembly checkpoint loss leads to neural apoptosis and reduced brain size"],"prefix":"10.1083","volume":"216","author":[{"given":"John S.","family":"Poulton","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 1"},{"name":"Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Cuningham","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-3987","authenticated-orcid":true,"given":"Mark","family":"Peifer","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 1"},{"name":"Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 3"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2017,3,28]]},"reference":[{"key":"2023072314072778300_bib1","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1016\/j.cell.2006.05.025","article-title":"Flies without centrioles","volume":"125","author":"Basto","year":"2006","journal-title":"Cell."},{"key":"2023072314072778300_bib2","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1016\/j.cell.2014.07.045","article-title":"Temporal patterning of neuroblasts controls Notch-mediated cell survival through regulation of Hid or Reaper","volume":"158","author":"Bertet","year":"2014","journal-title":"Cell."},{"key":"2023072314072778300_bib3","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1016\/j.cell.2006.01.038","article-title":"Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells","volume":"124","author":"Betschinger","year":"2006","journal-title":"Cell."},{"key":"2023072314072778300_bib4","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1534\/genetics.108.095141","article-title":"Drosophila asterless and vertebrate Cep152 are orthologs essential for centriole duplication","volume":"180","author":"Blachon","year":"2008","journal-title":"Genetics."},{"key":"2023072314072778300_bib5","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/j.cub.2005.03.052","article-title":"Recruitment of Mad2 to the kinetochore requires the Rod\/Zw10 complex","volume":"15","author":"Buffin","year":"2005","journal-title":"Curr. 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