{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:28:40Z","timestamp":1772771320524,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1046032"],"award-info":[{"award-number":["GNT1046032"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1162652"],"award-info":[{"award-number":["GNT1162652"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["FT120100193"],"award-info":[{"award-number":["FT120100193"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cancer Council","award":["GNT1101931"],"award-info":[{"award-number":["GNT1101931"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>WDR62 mutations that result in protein loss, truncation or single amino-acid substitutions are causative for human microcephaly, indicating critical roles in cell expansion required for brain development. WDR62 missense mutations that retain protein expression represent partial loss-of-function mutants that may therefore provide specific insights into radial glial cell processes critical for brain growth. Here we utilized CRISPR\/Cas9 approaches to generate three strains of WDR62 mutant mice; WDR62 V66M\/V66M and WDR62R439H\/R439H mice recapitulate conserved missense mutations found in humans with microcephaly, with the third strain being a null allele (WDR62stop\/stop). Each of these mutations resulted in embryonic lethality to varying degrees and gross morphological defects consistent with ciliopathies (dwarfism, anophthalmia and microcephaly). We find that WDR62 mutant proteins (V66M and R439H) localize to the basal body but fail to recruit CPAP. As a consequence, we observe deficient recruitment of IFT88, a protein that is required for cilia formation. This underpins the maintenance of radial glia as WDR62 mutations caused premature differentiation of radial glia resulting in reduced generation of neurons and cortical thinning. These findings highlight the important role of the primary cilium in neocortical expansion and implicate ciliary dysfunction as underlying the pathology of MCPH2 patients.<\/jats:p>","DOI":"10.1093\/hmg\/ddz281","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T07:10:58Z","timestamp":1574320258000},"page":"248-263","source":"Crossref","is-referenced-by-count":43,"title":["The association of microcephaly protein WDR62 with CPAP\/IFT88 is required for cilia formation and neocortical development"],"prefix":"10.1093","volume":"29","author":[{"given":"Belal","family":"Shohayeb","sequence":"first","affiliation":[{"name":"Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, St Lucia 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uda","family":"Ho","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, St Lucia 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne Y","family":"Yeap","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, St Lucia 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert G","family":"Parton","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia"},{"name":"Centre for Microscopy and Microanalysis, The University of Queensland, St Lucia 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S Sean","family":"Millard","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, St Lucia 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiheng","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Piper","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, St Lucia 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic C H","family":"Ng","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, St Lucia 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"2020020509130363800_ref1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.tig.2009.09.011","article-title":"Primary microcephaly: do all roads lead to Rome?","volume":"25","author":"Thornton","year":"2009","journal-title":"Trends Genet."},{"key":"2020020509130363800_ref2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1055\/s-0037-1601448","article-title":"Autosomal recessive primary microcephaly (MCPH): an update","volume":"48","author":"Zaqout","year":"2017","journal-title":"Neuropediatrics"},{"key":"2020020509130363800_ref3","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2009.10.036","article-title":"Centrioles, centrosomes, and cilia in health and disease","volume":"139","author":"Nigg","year":"2009","journal-title":"Cell"},{"key":"2020020509130363800_ref4","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":"2020020509130363800_ref5","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":"2020020509130363800_ref6","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":"Bilguvar","year":"2010","journal-title":"Nature"},{"key":"2020020509130363800_ref7","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/ng.682","article-title":"WDR62 is associated with the spindle pole and is mutated in human microcephaly","volume":"42","author":"Nicholas","year":"2010","journal-title":"Nat. Genet."},{"key":"2020020509130363800_ref8","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1038\/ncomms4885","article-title":"Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size","volume":"5","author":"Chen","year":"2014","journal-title":"Nat. Commun."},{"key":"2020020509130363800_ref9","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.neuron.2016.09.056","article-title":"Microcephaly proteins Wdr62 and Aspm define a mother centriole complex regulating centriole biogenesis, apical complex, and cell fate","volume":"92","author":"Jayaraman","year":"2016","journal-title":"Neuron"},{"key":"2020020509130363800_ref10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.celrep.2013.12.016","article-title":"Microcephaly-associated protein WDR62 regulates neurogenesis through JNK1 in the developing neocortex","volume":"6","author":"Xu","year":"2014","journal-title":"Cell. 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