Article

The nuclear receptor TLX is required for gliomagenesis within the adult neurogenic niche.

Department of Molecular Biology.
Molecular and Cellular Biology (Impact Factor: 5.04). 10/2012; DOI: 10.1128/MCB.01122-12
Source: PubMed

ABSTRACT Neural stem cells (NSCs) continually generate functional neurons in the adult brain. Due to their ability to proliferate, deregulated NSCs or their progenitors have been proposed as the cell-of-origin for a number of primary central nervous system neoplasms, including infiltrating gliomas. The orphan nuclear receptor TLX is required for proliferation of adult NSCs and its up-regulation promotes brain tumor formation. However, it is unknown whether TLX is required for gliomagenesis. We examined the genetic interactions between TLX and several tumor suppressors, as well as the role of TLX-dependent NSCs during gliomagenesis, using mouse models. Here, we show that TLX is essential for the proliferation of adult NSCs with single deletion of p21, p53, Pten, or combined deletion of Pten and p53. While brain tumors still form in Tlx-mutant mice, these tumors are less infiltrative and rarely associate with the adult neurogenic niches suggesting a non-stem cell origin. Taken together, these results indicate a critical role for TLX in NSC-dependent gliomagenesis and implicate TLX as a potential therapeutic target to inhibit the development of NSC-derived brain tumors.

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