Ninein is essential for the maintenance of the cortical progenitor character by anchoring the centrosome to microtubules

Hiroshi Shinohara, Nobuyuki Sakayori, Masanori Takahashi, Noriko Osumi

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

The mammalian cerebral cortex develops from proliferative apical progenitor cells (APs) that exhibit cell cycle-dependent nuclear movement (interkinetic nuclear migration; INM), which may be important for efficient and continuous production of neurons. The Pax6 transcription factor plays a major role in INMby regulating various downstreammolecules. We have previously observed abnormal INM and unstable localization of the centrosome in APs of the Pax6 homozygous mutant rat embryo. To understand the mechanisms of INM, we focused on the centrosomes of APs. One of the centrosomal proteins, ninein, is specifically localized in the centrosome of APs. We observed a dramatic downregulation of ninein in APs of the Pax6 mutant. Moreover, knockdown of ninein by RNAi induced ectopic distribution of reduced numbers of BrdUpositive (S-phase) and PH3-positive (M-phase) cells. Furthermore, time-lapsed imaging demonstrated that knockdown of ninein in vivo induced abnormal INM. Finally, we observed impaired microtubule regrowth in neural progenitors taken from Pax6 homozygous mutant rat embryos, which was recovered by via ninein overexpression. We also found that ninein knockdown enlarged the surface size area of apical endfeet of the APs. Our results suggest that ninein plays a role in the molecular machinery essential for INM by connecting microtubules to the centrosome.

Original languageEnglish
Pages (from-to)739-749
Number of pages11
JournalBiology Open
Volume2
Issue number7
DOIs
Publication statusPublished - 2013 Jul 15

Keywords

  • Centrosome
  • Cortical progenitor cells
  • Interkinetic nuclear migration
  • Mictrotubules
  • Ninein
  • Pax6
  • Rat

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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