Neurodevelopmental Abnormalities in Neurosphere-Derived Neural Stem Cells From SMN-depleted Mice

J Neurosci Res. 2008 Oct;86(13):2839-47. doi: 10.1002/jnr.21743.


Spinal muscular atrophy (SMA) is a genetic disorder caused by depletion of survival motor neuron (SMN) protein and characterized by degeneration of alpha-motor neurons in the spinal cord. We investigated the morphology and differentiation of neurosphere-derived neural stem cells (NSCs) generated from the brains of a hypomorphic series of SMA mice. Neurospheres from the Smn(-/-);SMN2 mice, which represent a model of very severe SMA, produced NSCs with increased proliferation during growth and differentiation. These cells produced fewer Tuj1-positive neuronal cells, which displayed morphological alterations and had fewer and shorter neurites. The decrease in the number of Tuj1-positive cells was not a result of enhanced apoptosis but was accompanied by an increase in the number of nestin-positive cells. These results provide insight into the most severe model of SMA, in which SMN is nearly completely depleted, and suggest that SMN has a role in neurodevelopment as well as in neuromaintenance. Our work raises the possibility that SMN depletion affects neurodevelopment and neuromaintenance to varying extents, leading to SMA pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Blotting, Western
  • Cell Differentiation / physiology*
  • Cell Proliferation
  • Fluorescent Antibody Technique
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Transgenic
  • Neurons / cytology*
  • Neurons / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Survival of Motor Neuron 1 Protein / genetics
  • Survival of Motor Neuron 1 Protein / metabolism*


  • Smn1 protein, mouse
  • Survival of Motor Neuron 1 Protein