Cerebellar granule cell precursors can differentiate into astroglial cells

Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1211-6. doi: 10.1073/pnas.0307972100. Epub 2004 Jan 26.

Abstract

During CNS development, multipotent neural stem cells give rise first to various kinds of specified precursor cells, which proliferate extensively before terminally differentiating into either neurons or glial cells. It is still not clear, however, whether the specified precursor cells are irreversibly determined to differentiate into their particular cell types. In this study, we show that isolated mouse cerebellar granule cell precursors from the outermost, proliferative zone of the external germinal layer can differentiate into astroglial cells when exposed to sonic hedgehog (Shh) and bone morphogenetic proteins. These induced cells initially expressed both glial fibrillary acidic protein and neuronal markers, but they then lost their neuronal markers and acquired S100-beta, a marker of differentiated astroglial cells. These results indicate that at least some granule cell precursors are not irreversibly committed to neuronal development but can be induced to differentiate into astroglial cells by appropriate extracellular signals.

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / pharmacology
  • Cell Differentiation
  • Cell Division / drug effects
  • Cerebellum / cytology*
  • Glial Fibrillary Acidic Protein / analysis
  • Hedgehog Proteins
  • Mice
  • Mice, Inbred C57BL
  • Stem Cells / cytology*
  • Trans-Activators / pharmacology
  • Transforming Growth Factor beta*

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Glial Fibrillary Acidic Protein
  • Hedgehog Proteins
  • Trans-Activators
  • Transforming Growth Factor beta