Paired Related Homeobox Protein 1 is a Regulator of Stemness in Adult Neural Stem/Progenitor Cells
- 1Division of Functional Genomics, Center for Frontier Life Science, Nagasaki University, Nagasaki 852-8102, Japan and
- 2Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037
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Author contributions: K.S. and F.H.G. designed research; K.S. and G.D.C. performed research; K.S. and G.D.C. contributed unpublished reagents/analytic tools; K.S. analyzed data; K.S. and F.H.G. wrote the paper.
Abstract
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.
- Received September 26, 2012.
- Revision received December 21, 2012.
- Accepted January 12, 2013.
- Copyright © 2013 the authors 0270-6474/13/334066-10$15.00/0
