Requirement for COUP-TFI and II in the temporal specification of neural stem cells in CNS development

Hayato Naka, Shiho Nakamura, Takuya Shimazaki, Hideyuki Okano

Research output: Contribution to journalArticle

145 Citations (Scopus)


In the developing CNS, subtypes of neurons and glial cells are generated according to a schedule that is defined by cell-intrinsic mechanisms that function at the progenitor-cell level. However, no critical molecular switch for the temporal specification of CNS progenitor cells has been identified. We found that chicken ovalbumin upstream promoter-transcription factor I and II (Coup-tfI and Coup-tfII, also known as Nr2f1 and Nr2f2) are required for the temporal specification of neural stem/progenitor cells (NSPCs), including their acquisition of gliogenic competence, as demonstrated by their responsiveness to gliogenic cytokines. COUP-TFI and II are transiently co-expressed in the ventricular zone of the early embryonic CNS. The double knockdown of Coup-tfI/II in embryonic stem cell (ESC)-derived NSPCs and the developing mouse forebrain caused sustained neurogenesis and the prolonged generation of early-born neurons. These findings reveal a part of the timer mechanisms for generating diverse types of neurons and glial cells during CNS development.

Original languageEnglish
Pages (from-to)1014-1023
Number of pages10
JournalNature Neuroscience
Issue number9
Publication statusPublished - 2008 Sep 1


ASJC Scopus subject areas

  • Neuroscience(all)

Cite this