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

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

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  • 1Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.


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.

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