Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone

Stem Cells. 2016 Aug;34(8):2115-29. doi: 10.1002/stem.2374. Epub 2016 Apr 21.


Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thus, our work uncovers a novel function of Prox1 as a fate determinant for oligodendrocytes in the adult mammalian brain. These data indicate that the neurogenic and oligodendrogliogenic lineages in the two adult neurogenic niches exhibit a distinct requirement for Prox1, being important for neurogenesis in the DG but being indispensable for oligodendrogliogenesis in the SVZ. Stem Cells 2016;34:2115-2129.

Keywords: Adult neurogenesis; Neural stem cells; Oligodendrocytes; Prox1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism*
  • Animals
  • Body Patterning / genetics
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Cell Movement / genetics
  • Cells, Cultured
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Homeodomain Proteins / metabolism*
  • Lateral Ventricles / cytology*
  • Mice
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Neurogenesis / genetics
  • Olfactory Bulb / cytology
  • Olfactory Bulb / metabolism
  • Oligodendrocyte Transcription Factor 2 / genetics
  • Oligodendrocyte Transcription Factor 2 / metabolism
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Tumor Suppressor Proteins / metabolism*


  • Homeodomain Proteins
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2
  • Receptors, Notch
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein