Increase in proliferation and differentiation of neural progenitor cells isolated from postnatal and adult mice brain by Wnt-3a and Wnt-5a

Mol Cell Biochem. 2006 Aug;288(1-2):17-28. doi: 10.1007/s11010-005-9113-3. Epub 2006 Apr 1.

Abstract

Wnt signaling is implicated in the control of cell growth and differentiation during CNS development. These findings are based on studies of mouse and chick models. However, the action of Wnt signaling, at the cellular level, is poorly understood. In this study, we investigated the roles of Wnt-3a and Wnt-5a on differentiation and proliferation of postnatal neural progenitor cells (NPCs) in mice.NPCs were isolated from the subventricular zone (SVZ) of PN-1 and adult ICR mice. Plasmids containing active Wnt-3a or Wnt-5a were transfected to NPCs; their effects on the formation of neurospheres and differentiation into neuronal cells were then determined. Transfection of Wnt-3a and Wnt-5a plasmids promoted regeneration of neurospheres and differentiation into Map2-positive cells, and decreased differentiation into GFAP-positive cells. The conditioned media obtained from Wnt-3a or Wnt-5a transfected NPCs showed similar effects on differentiation of NPCs with cDNA transfection, although the magnitude of stimulatory effect was less than that by plasmid transfection. Wnt-3a and Wnt-5a transfection did not affect Brdu incorporation of neuronal or glial progenitors in differentiation media. Wnt-3a and Wnt-5a plasmid transfection and the treatment of Wnt-3a and Wnt-5a conditioned media increased beta-catenin levels in NPCs. Wnt-3a had a greater effect on beta-catenin levels than Wnt-5a. The PKC inhibitor completely blocked the Wnt-5a effect on neuronal differentiation in NPCs. These findings suggest that Wnt-3a and Wnt-5a each have distinct effects on the proliferation and differentiation of NPCs in postnatal mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Brain / cytology*
  • Brain / growth & development
  • Brain / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Immunohistochemistry
  • Mice
  • Neurons / cytology*
  • Neurons / metabolism
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Proto-Oncogene Proteins / pharmacology
  • Proto-Oncogene Proteins / physiology*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transfection
  • Type C Phospholipases / metabolism
  • Wnt Proteins / pharmacology
  • Wnt Proteins / physiology*
  • Wnt-5a Protein
  • Wnt3 Protein
  • Wnt3A Protein
  • beta Catenin / metabolism

Substances

  • Proto-Oncogene Proteins
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt3 Protein
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • Wnt5a protein, mouse
  • beta Catenin
  • Protein Kinase C
  • Type C Phospholipases