Wdr62 is associated with the spindle pole and is mutated in human microcephaly

ABSTRACT Autosomal recessive primary microcephaly (MCPH) is a disorder of neurodevelopment resulting in a small brain1,2. We identified _WDR62_ as the second most common cause of MCPH after

finding homozygous missense and frame-shifting mutations in seven MCPH families. In human cell lines, we found that WDR62 is a spindle pole protein, as are ASPM and STIL, the MCPH7 and MCHP7

proteins3,4,5. Mutant WDR62 proteins failed to localize to the mitotic spindle pole. In human and mouse embryonic brain, we found that WDR62 expression was restricted to neural precursors

undergoing mitosis. These data lend support to the hypothesis that the exquisite control of the cleavage furrow orientation in mammalian neural precursor cell mitosis, controlled in great

part by the centrosomes and spindle poles, is critical both in causing MCPH when perturbed and, when modulated, generating the evolutionarily enlarged human brain6,7,8,9. Access through your

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BEING VIEWED BY OTHERS RRP7A LINKS PRIMARY MICROCEPHALY TO DYSFUNCTION OF RIBOSOME BIOGENESIS, RESORPTION OF PRIMARY CILIA, AND NEUROGENESIS Article Open access 16 November 2020 GENETIC

INTERACTION BETWEEN PLK1 AND DOWNSTREAM MCPH PROTEINS IN THE CONTROL OF CENTROSOME ASYMMETRY AND CELL FATE DURING NEURAL PROGENITOR DIVISION Article 20 January 2022 ENDOSOMAL TRAFFICKING

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Scholar  Download references ACKNOWLEDGEMENTS The authors would like to thank the research families for their participation in this project and the Wellcome Trust, Medical Research Council,

Action Research and the Higher Education Commission of Pakistan for funding (to A.K.N., M.K., O.P.C., J.J.C., G.T. and E.R.). J.D. was supported by the Belgian Kids' Fund. M.A. was

supported by grants from the Fonds Erasme and the Belgian Fonds de la Recherche Scientifique Médicale (FRSM). We thank S. Strollo for expert technical assistance. We thank the Medical

Research Council (MRC)-Wellcome Trust Human Developmental Biology Resource (HDBR), Newcastle for providing the human tissue for the expression studies. AUTHOR INFORMATION Author notes *

Adeline K Nicholas, Maryam Khurshid and Julie Désir: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Department of Medical Genetics, Cambridge Institute for

Medical Research, University of Cambridge, Cambridge, UK Adeline K Nicholas, Maryam Khurshid, Ofélia P Carvalho, James J Cox, Gemma Thornton & C Geoffrey Woods * Department of Medical

Genetics, Hôpital Erasme and Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université libre de Bruxelles (IRIBHM), ULB, Brussels, Belgium Julie Désir & 

Marc Abramowicz * Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan Rizwana Kausar, Muhammad Ansar & Wasim Ahmad * Department of

Genetics, Robert Debré University Hospital, Paris, France Alain Verloes & Sandrine Passemard * Department of Child Neurology, Assistance publique-Hôpitaux de Paris (AP-HP) Robert Debré

University Hospital, Paris, France Sandrine Passemard * University of Liège Medical School and Department of Pediatrics, La Citadelle University Hospital, Liège, Belgium Jean-Paul Misson *

Institute of Human Genetics, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK Susan Lindsay * Cancer Research UK Cambridge Research Institute, Li

Ka Shing Centre, Cambridge, UK Fanni Gergely * Department of Human Genetics, University of Chicago, Chicago, Illinois, USA William B Dobyns * Microcephaly and Neurogenesis research group,

Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds, UK Emma Roberts Authors * Adeline K Nicholas View author publications You can also search for this author

inPubMed Google Scholar * Maryam Khurshid View author publications You can also search for this author inPubMed Google Scholar * Julie Désir View author publications You can also search for

this author inPubMed Google Scholar * Ofélia P Carvalho View author publications You can also search for this author inPubMed Google Scholar * James J Cox View author publications You can

also search for this author inPubMed Google Scholar * Gemma Thornton View author publications You can also search for this author inPubMed Google Scholar * Rizwana Kausar View author

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View author publications You can also search for this author inPubMed Google Scholar * Alain Verloes View author publications You can also search for this author inPubMed Google Scholar *

Sandrine Passemard View author publications You can also search for this author inPubMed Google Scholar * Jean-Paul Misson View author publications You can also search for this author

inPubMed Google Scholar * Susan Lindsay View author publications You can also search for this author inPubMed Google Scholar * Fanni Gergely View author publications You can also search for

this author inPubMed Google Scholar * William B Dobyns View author publications You can also search for this author inPubMed Google Scholar * Emma Roberts View author publications You can

also search for this author inPubMed Google Scholar * Marc Abramowicz View author publications You can also search for this author inPubMed Google Scholar * C Geoffrey Woods View author

publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS The following authors contributed to the design of the study: A.K.N., M.K., J.J.C., F.G., E.R., M.

Abramowicz and C.G.W. The following authors generated experimental data: A.K.N., M.K., J.D., O.P.C., G.T., R.K., M. Ansar, F.G., W.B.D., E.R. and C.G.W. Reagents were contributed by R.K., M.

Abramowicz, W.A., A.L., S.P., J.-P.M., S.L., M. Abramowicz and C.G.W. The paper was written by A.K.N., M.K., O.P.C., J.J.C., W.A., S.L., F.G., W.B.D. and C.G.W. CORRESPONDING AUTHORS

Correspondence to Marc Abramowicz or C Geoffrey Woods. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY

TEXT AND FIGURES Supplementary Table 1 and Supplementary Figures 1–7 (PDF 796 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nicholas, A., Khurshid,

M., Désir, J. _et al._ _WDR62_ is associated with the spindle pole and is mutated in human microcephaly. _Nat Genet_ 42, 1010–1014 (2010). https://doi.org/10.1038/ng.682 Download citation *

Received: 27 May 2010 * Accepted: 10 September 2010 * Published: 03 October 2010 * Issue Date: November 2010 * DOI: https://doi.org/10.1038/ng.682 SHARE THIS ARTICLE Anyone you share the

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