Wnt-3a and Wnt-3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling

J Neurosci Res. 2010 Nov 1;88(14):3011-23. doi: 10.1002/jnr.22464.


Wnt factors regulate neural stem cell development and neuronal connectivity. Here we investigated whether Wnt-3a and Wnt-3, expressed in the developing spinal cord, regulate proliferation and the neuronal differentiation of spinal cord neural precursors (SCNP). Wnt-3a promoted a sustained increase of SCNP proliferation and decreased the expression of cyclin-dependent kinase inhibitors. In contrast, Wnt-3 transiently enhanced SCNP proliferation and increased neurogenesis through β-catenin signaling. Furthermore, both Wnt-3a and Wnt-3 stimulated neurite outgrowth in SCNP-derived neurons through β-catenin- and TCF4-dependent transcription. Glycogen synthase kinase-3β inhibitors mimicked Wnt signaling and promoted neurite outgrowth in established cultures. We conclude that Wnt-3a and Wnt-3 factors signal through the canonical Wnt/β-catenin pathway to regulate different aspects of SCNP development. These findings may be of therapeutic interest for the treatment of neurodegenerative diseases and nerve injury.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Line
  • Cell Proliferation
  • Cells, Cultured
  • HEK293 Cells
  • Humans
  • Mice
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurites / metabolism*
  • Neurites / physiology
  • Neurogenesis / physiology*
  • Rats
  • Signal Transduction / physiology*
  • Spinal Cord / cytology
  • Spinal Cord / embryology*
  • Wnt Proteins / physiology*
  • Wnt3 Protein
  • Wnt3A Protein
  • beta Catenin / physiology


  • WNT3 protein, human
  • WNT3A protein, human
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3 protein, mouse
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • beta Catenin