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

Nat Neurosci. 2008 Sep;11(9):1014-23. doi: 10.1038/nn.2168.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • COUP Transcription Factor I / genetics
  • COUP Transcription Factor I / metabolism*
  • COUP Transcription Factor II / genetics
  • COUP Transcription Factor II / metabolism*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Central Nervous System / cytology*
  • Central Nervous System / drug effects
  • Central Nervous System / embryology*
  • Chromatin Immunoprecipitation / methods
  • Cytokines / metabolism
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins / genetics
  • Mice
  • Mice, Inbred ICR
  • Mutation / genetics
  • Neurogenesis / genetics
  • Neuroglia / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Organ Culture Techniques
  • RNA, Small Interfering / pharmacology
  • Stem Cells / drug effects
  • Stem Cells / physiology*
  • Time Factors
  • Transfection / methods
  • Tubulin / metabolism

Substances

  • COUP Transcription Factor I
  • COUP Transcription Factor II
  • Cytokines
  • Glial Fibrillary Acidic Protein
  • RNA, Small Interfering
  • Tubulin
  • beta3 tubulin, mouse
  • Green Fluorescent Proteins
  • Bromodeoxyuridine