title: Paired related homeobox protein 1 is a regulator of stemness in adult neural stem/progenitor cells.
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.
authors: Division of Functional Genomics, Center for Frontier Life Science, Nagasaki University, Nagasaki 852-8102, Japan. shimozak@nagasakiu.ac.jp
authors: Koji
authors: K
authors: Shimozaki
authors: Gregory D
authors: GD
authors: Clemenson
authors: Fred H
authors: FH
authors: Gage
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001973:Bromodeoxyuridine; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D016548:Prosencephalon / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C489936:Prrx1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; C527784:Sox2 protein, rat; D049452:Green Fluorescent Proteins; D053148:Caspase 3; D001973:Bromodeoxyuridine