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Here, we inactivated the minor spliceosome in the developing mouse cortex (pallium) by ablating Rnu11, which encodes the crucial minor spliceosome small nuclear RNA (snRNA) U11. Rnu11 conditional knockout mice were born with microcephaly, which was caused by the death of self-amplifying radial glial cells (RGCs), while intermediate progenitor cells and neurons were produced. RNA sequencing suggested that this cell death was mediated by upregulation of p53 (Trp53 \u2013 Mouse Genome Informatics) and DNA damage, which were both observed specifically in U11-null RGCs. Moreover, U11 loss caused elevated minor intron retention in genes regulating the cell cycle, which was consistent with fewer RGCs in S-phase and cytokinesis, alongside prolonged metaphase in RGCs. In all, we found that self-amplifying RGCs are the cell type most sensitive to loss of minor splicing. Together, these findings provide a potential explanation of how disruption of minor splicing might cause microcephaly in MOPD1.<\/jats:p>","DOI":"10.1242\/dev.166322","type":"journal-article","created":{"date-parts":[[2018,8,9]],"date-time":"2018-08-09T07:16:20Z","timestamp":1533798980000},"source":"Crossref","is-referenced-by-count":61,"title":["Minor spliceosome inactivation causes microcephaly, owing to cell cycle defects and death of self-amplifying radial glial cells"],"prefix":"10.1242","volume":"145","author":[{"given":"Marybeth","family":"Baumgartner","sequence":"first","affiliation":[{"name":"University of Connecticut 1 Physiology and Neurobiology Department , , Storrs, CT 06269 , USA"},{"name":"Connecticut Institute for the Brain and Cognitive Sciences, University of Connecticut 2 , Storrs, CT 06269 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk M.","family":"Olthof","sequence":"additional","affiliation":[{"name":"University of Connecticut 1 Physiology and Neurobiology Department , , Storrs, CT 06269 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela S.","family":"Aquino","sequence":"additional","affiliation":[{"name":"University of Connecticut 1 Physiology and Neurobiology Department , , Storrs, CT 06269 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katery C.","family":"Hyatt","sequence":"additional","affiliation":[{"name":"University of Connecticut 1 Physiology and Neurobiology Department , , Storrs, CT 06269 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lemoine","sequence":"additional","affiliation":[{"name":"University of Connecticut 1 Physiology and Neurobiology Department , , Storrs, CT 06269 , USA"},{"name":"College of Medicine, University of Illinois 3 , Chicago, IL 60612 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Drake","sequence":"additional","affiliation":[{"name":"University of Connecticut 1 Physiology and Neurobiology Department , , Storrs, CT 06269 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Sturrock","sequence":"additional","affiliation":[{"name":"University of Connecticut 1 Physiology and Neurobiology Department , , Storrs, CT 06269 , USA"},{"name":"Biological and Biomedical Sciences Program 4 , Harvard Medical School, Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhut","family":"Nguyen","sequence":"additional","affiliation":[{"name":"University of Connecticut 1 Physiology and Neurobiology Department , , Storrs, CT 06269 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"al Seesi","sequence":"additional","affiliation":[{"name":"University of Connecticut 5 Computer Science Engineering Department , , Storrs, CT 06269 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7197-912X","authenticated-orcid":false,"given":"Rahul N.","family":"Kanadia","sequence":"additional","affiliation":[{"name":"University of Connecticut 1 Physiology and Neurobiology Department , , Storrs, CT 06269 , USA"},{"name":"Institute of Systems Genomics, University of Connecticut 6 , Storrs, CT 06269 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2018,8,28]]},"reference":[{"key":"2024061113464268100_DEV166322C1","doi-asserted-by":"publisher","first-page":"D110","DOI":"10.1093\/nar\/gkl796","article-title":"U12DB: a database of orthologous U12-type spliceosomal introns","volume":"35","author":"Alioto","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2024061113464268100_DEV166322C2","doi-asserted-by":"publisher","first-page":"5611","DOI":"10.1038\/ncomms6611","article-title":"Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex","volume":"5","author":"Arn\u00f2","year":"2014","journal-title":"Nat. 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