Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates

Yuji Tsunekawa, Joanne M. Britto, Masanori Takahashi, Franck Polleux, Seong Seng Tan, Noriko Osumi

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Asymmetric cell division plays an indispensable role during corticogenesis for producing new neurons while maintaining a self-renewing pool of apical progenitors. The cellular and molecular determinants favouring asymmetric division are not completely understood. Here, we identify a novel mechanism for generating cellular asymmetry through the active transportation and local translation of Cyclin D2 mRNA in the basal process. This process is regulated by a unique cis-regulatory sequence found in the 3′ untranslated region (3′UTR) of the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned daughter cell with the basal process confers renewal of the apical progenitor after asymmetric division. Conversely, depletion of Cyclin D2 in the apically positioned daughter cell results in terminal neuronal differentiation. We demonstrate that Cyclin D2 is also expressed in the developing human cortex within similar domains, thus indicating that its role as a fate determinant is ancient and conserved.

Original languageEnglish
Pages (from-to)1879-1892
Number of pages14
JournalEMBO Journal
Volume31
Issue number8
DOIs
Publication statusPublished - 2012 Apr 18

Keywords

  • Cyclin D2
  • asymmetric cell division
  • corticogenesis
  • mRNA subcellular localization
  • neuronal differentiation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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