Orphan nuclear receptor TLX regulates astrogenesis by modulating BMP signaling

Song Qin, Wenze Niu, Nida Iqbal, Derek K. Smith, Chun Li Zhang

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Neural stem cells (NSCs) are self-renewing multipotent progenitors that generate both neurons and glia. The precise control of NSC behavior is fundamental to the architecture and function of the central nervous system. We previously demonstrated that the orphan nuclear receptor TLX is required for postnatal NSC activation and neurogenesis in the neurogenic niche. Here, we show that TLX modulates bone morphogenetic protein (BMP)-SMAD signaling to control the timing of postnatal astrogenesis. Genes involved in the BMP signaling pathway, such as Bmp4, Hes1, and Id3, are upregulated in postnatal brains lacking Tlx. Chromatin immunoprecipitation and electrophoretic mobility shift assays reveal that TLX can directly bind the enhancer region of Bmp4. In accordance with elevated BMP signaling, the downstream effectors SMAD1/5/8 are activated by phosphorylation in Tlx mutant mice. Consequently, Tlx mutant brains exhibit an early appearance and increased number of astrocytes with marker expression of glial fibrillary acidic protein (GFAP) and S100B. Taken together, these results suggest that TLX tightly controls postnatal astrogenesis through the modulation of BMP-SMAD signaling pathway activity.

Original languageEnglish (US)
Article number74
JournalFrontiers in Neuroscience
Issue number8 APR
DOIs
StatePublished - 2014

Keywords

  • Astrogenesis
  • BMP-SMAD signaling
  • Neural stem cells
  • Neurogenesis
  • Nuclear receptor
  • Tlx

ASJC Scopus subject areas

  • Neuroscience(all)

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