Mitotic spindle regulation by Nde1 controls cerebral cortical size.
Ablation of the LIS1-interacting protein Nde1 (formerly mNudE) in mouse produces a small brain (microcephaly), with the most dramatic reduction affecting the cerebral cortex. While cortical lamination is mostly preserved, the mutant cortex has fewer neurons and very thin superficial cortical layers (II to IV). BrdU birthdating revealed retarded and modestly disorganized neuronal migration; however, more dramatic defects on mitotic progression, mitotic orientation, and mitotic chromosome localization in cortical progenitors were observed in Nde1 mutant embryos. The small cerebral cortex seems to reflect both reduced progenitor cell division and altered neuronal cell fates. In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. Our data show that mitotic spindle function and orientation are essential for normal development of mammalian cerebral cortex.
Feng
Yuanyi
Y
Department of Neurology, Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Walsh
Christopher A
CA
D000818:Animals; D015139:Blotting, Southern; D019556:COS Cells; D002352:Carrier Proteins / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000196:embryology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051379:Mice; D008831:Microcephaly / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D008941:Spindle Apparatus / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology
D002352:Carrier Proteins; C421108:NDEL1 protein, human