title: 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 brain. 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 proteins. 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 brain.
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Adeline K
authors.initials: AK
authors.lastname: Nicholas
authors.forename: Maryam
authors.initials: M
authors.lastname: Khurshid
authors.forename: Julie
authors.initials: J
authors.lastname: Désir
authors.forename: Ofélia P
authors.initials: OP
authors.lastname: Carvalho
authors.forename: James J
authors.initials: JJ
authors.lastname: Cox
authors.forename: Gemma
authors.initials: G
authors.lastname: Thornton
authors.forename: Rizwana
authors.initials: R
authors.lastname: Kausar
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Sandrine
authors.initials: S
authors.lastname: Passemard
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Misson
authors.forename: Susan
authors.initials: S
authors.lastname: Lindsay
authors.forename: Fanni
authors.initials: F
authors.lastname: Gergely
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Emma
authors.initials: E
authors.lastname: Roberts
authors.forename: Marc
authors.initials: M
authors.lastname: Abramowicz
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Woods
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006367:HeLa Cells / Q000166:cytology; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008831:Microcephaly / Q000235:genetics*; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D008941:Spindle Apparatus / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; C552527:WDR62 protein, human