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

TITLE=Orphan nuclear receptor TLX regulates astrogenesis by modulating BMP signaling

JOURNAL=Frontiers in Neuroscience

VOLUME=8

YEAR=2014

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2014.00074

DOI=10.3389/fnins.2014.00074

ISSN=1662-453X

ABSTRACT=<p>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 <italic>Bmp4</italic>, <italic>Hes1</italic>, and <italic>Id3</italic>, are upregulated in postnatal brains lacking <italic>Tlx</italic>. Chromatin immunoprecipitation and electrophoretic mobility shift assays reveal that TLX can directly bind the enhancer region of <italic>Bmp4</italic>. In accordance with elevated BMP signaling, the downstream effectors SMAD1/5/8 are activated by phosphorylation in <italic>Tlx</italic> mutant mice. Consequently, <italic>Tlx</italic> 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.</p>