Activation of postnatal neural stem cells requires nuclear receptor TLX

Wenze Niu, Yuhua Zou, Chengcheng Shen, Chun Li Zhang

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Neural stem cells (NSCs) continually produce new neurons in postnatal brains. However, the majority of these cells stay in a nondividing, inactive state. The molecular mechanism that is required for these cells to enter proliferation still remains largely unknown. Here, we show that nuclear receptor TLX (NR2E1) controls the activation status of postnatal NSCs in mice. Lineage tracing indicates that TLXexpressing cells give rise to both activated and inactive postnatal NSCs. Surprisingly, loss of TLX function does not result in spontaneous glial differentiation, but rather leads to a precipitous age-dependent increase of inactive cells with marker expression and radial morphology for NSCs. These inactive cells are mispositioned throughout the granular cell layer of the dentate gyrus during development and can proliferate again after reintroduction of ectopic TLX. RNA-seq analysis of sorted NSCs revealed a TLX-dependent global expression signature, which includes the p53 signaling pathway. TLX regulates p21 expression in a p53-dependent manner, and acute removal of p53 can rescue the proliferation defect of TLX-null NSCs in culture. Together, these findings suggest that TLX acts as an essential regulator that ensures the proliferative ability of postnatal NSCs by controlling their activation through genetic interaction with p53 and other signaling pathways.

Original languageEnglish (US)
Pages (from-to)13816-13828
Number of pages13
JournalJournal of Neuroscience
Volume31
Issue number39
DOIs
StatePublished - Sep 28 2011

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Neural Stem Cells
Cytoplasmic and Nuclear Receptors
Dentate Gyrus
Neuroglia
Cell Culture Techniques
RNA
Neurons
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activation of postnatal neural stem cells requires nuclear receptor TLX. / Niu, Wenze; Zou, Yuhua; Shen, Chengcheng; Zhang, Chun Li.

In: Journal of Neuroscience, Vol. 31, No. 39, 28.09.2011, p. 13816-13828.

Research output: Contribution to journalArticle

Niu, Wenze ; Zou, Yuhua ; Shen, Chengcheng ; Zhang, Chun Li. / Activation of postnatal neural stem cells requires nuclear receptor TLX. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 39. pp. 13816-13828.
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