Paired Related Homeobox Protein 1 is a Regulator of Stemness in Adult Neural Stem/Progenitor Cells

被引：49
作者：
Shimozaki, Koji [1 ]
Clemenson, Gregory D., Jr. [2 ]
Gage, Fred H. [2 ]
机构：
[1] Nagasaki Univ, Ctr Frontier Life Sci, Div Funct Genom, Nagasaki 8528102, Japan
[2] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
来源：
JOURNAL OF NEUROSCIENCE | 2013年 / 33卷 / 09期
基金：
日本学术振兴会;
关键词：
SOX2-DEPENDENT REGULATION; HOMEODOMAIN PROTEIN; GENE-EXPRESSION; SONIC HEDGEHOG; MAINTENANCE; PAX6; ROLES; SOX; DIFFERENTIATION; PROLIFERATION;
D O I：
10.1523/JNEUROSCI.4586-12.2013
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Newborn neurons are generated from neural stem cells (NSCs) in two major niches of the adult brain. Maintenance of self-renewal and multipotency of adult NSCs is controlled by multiple transcription factor networks. We show here that paired related homeobox protein Prx1 (MHox1/Prrx1) plays an important role in the maintenance of adult NSCs. Prx1 works with the transcription factor Sox2 as a coactivator, and depletion of Prx1 in cultured adult mouse NSCs reduces their self-renewal. In addition, we find that Prx1 protein is expressed in Sox2(+)/GFAP(+)/Nestin(+) astrocytes in the germinal regions of the adult mouse forebrain. The continuous expression of Prx1 in proliferating adult mouse hippocampal stem/progenitor cells in vivo leads to the generation of radial/horizontal-shaped astrocyte progenitor- and oligodendrocyte progenitor-like cells with no newborn neurons in the neurogenic niche. These data suggest that Prx1 plays an important role as a key switch for neural cell lineage determination and the maintenance of the self-renewal of adult NSCs at several stages in the adult brain.
引用
收藏
页码：4066 / 4075
页数：10
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