Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate

Neuron. 2016 Nov 23;92(4):813-828. doi: 10.1016/j.neuron.2016.09.056. Epub 2016 Oct 27.


Mutations in several genes encoding centrosomal proteins dramatically decrease the size of the human brain. We show that Aspm (abnormal spindle-like, microcephaly-associated) and Wdr62 (WD repeat-containing protein 62) interact genetically to control brain size, with mice lacking Wdr62, Aspm, or both showing gene dose-related centriole duplication defects that parallel the severity of the microcephaly and increased ectopic basal progenitors, suggesting premature delamination from the ventricular zone. Wdr62 and Aspm localize to the proximal end of the mother centriole and interact physically, with Wdr62 required for Aspm localization, and both proteins, as well as microcephaly protein Cep63, required to localize CENPJ/CPAP/Sas-4, a final common target. Unexpectedly, Aspm and Wdr62 are required for normal apical complex localization and apical epithelial structure, providing a plausible unifying mechanism for the premature delamination and precocious differentiation of progenitors. Together, our results reveal links among centrioles, apical proteins, and cell fate, and illuminate how alterations in these interactions can dynamically regulate brain size.

Keywords: Aspm; Wdr62; apical complex; maternal centriole.

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / embryology*
  • Brain / metabolism
  • Calmodulin-Binding Proteins / genetics*
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Centrioles / metabolism*
  • Immunoprecipitation
  • Mass Spectrometry
  • Mice
  • Microcephaly / genetics*
  • Microtubule-Associated Proteins / genetics*
  • Mouse Embryonic Stem Cells
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Organelle Biogenesis*


  • ASPM protein, mouse
  • Calmodulin-Binding Proteins
  • Cell Cycle Proteins
  • Cenpj protein, mouse
  • Cep63 protein, mouse
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • WDR62 protein, mouse