Paired related homeobox protein 1 is a regulator of stemness in adult neural stem/progenitor cells

J Neurosci. 2013 Feb 27;33(9):4066-75. doi: 10.1523/JNEUROSCI.4586-12.2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / physiology*
  • Animals
  • Astrocytes / physiology
  • Bromodeoxyuridine
  • Caspase 3 / metabolism
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Neurons / physiology*
  • Oligonucleotide Array Sequence Analysis
  • Prosencephalon / cytology
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Rats
  • SOXB1 Transcription Factors / metabolism*
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Prrx1 protein, mouse
  • RNA, Messenger
  • RNA, Small Interfering
  • SOXB1 Transcription Factors
  • Sox2 protein, rat
  • Green Fluorescent Proteins
  • Caspase 3
  • Bromodeoxyuridine