Cortical excitatory neurons become protected from cell division during neurogenesis in an RB family-dependent manner

Mio Oshikawa, Kei Okada, Kazunori Nakajima, Itsuki Ajioka

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cell cycle dysregulation leads to abnormal proliferation and cell death in a context-specific manner. Cell cycle progression driven via the Rb pathway forces neurons to undergo S-phase, resulting in cell death associated with the progression of neuronal degeneration. Nevertheless, some Rb-and Rb family (Rb, p107 and p130)-deficient differentiating neurons can proliferate and form tumors. Here, we found in mouse that differentiating cerebral cortical excitatory neurons underwent S-phase progression but not cell division after acute Rb family inactivation in differentiating neurons. However, the differentiating neurons underwent cell division and proliferated when Rb family members were inactivated in cortical progenitors. Differentiating neurons generated from Rb-/-; p107-/-; p130-/- (Rb-TKO) progenitors, but not acutely inactivated Rb-TKO differentiating neurons, activated the DNA double-strand break (DSB) repair pathway without increasing trimethylation at lysine 20 of histone H4 (H4K20), which has a role in protection against DNA damage. The activation of the DSB repair pathway was essential for the cell division of Rb-TKO differentiating neurons. These results suggest that newly born cortical neurons from progenitors become epigenetically protected from DNA damage and cell division in an Rb family-dependent manner.

Original languageEnglish
Pages (from-to)2310-2320
Number of pages11
JournalDevelopment (Cambridge)
Volume140
Issue number11
DOIs
Publication statusPublished - 2012 Jun 1

Keywords

  • Cell cycle
  • Cerebral cortical neurons
  • DNA damage
  • Differentiation
  • Mouse
  • Proliferation
  • Retinoblastoma protein

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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