Retrovirally transduced NCAM140 facilitates neuronal fate choice of hippocampal progenitor cells

J Neurochem. 2005 Jul;94(2):417-24. doi: 10.1111/j.1471-4159.2005.03208.x.

Abstract

Neural cell adhesion molecule (NCAM) influences proliferation and differentiation of neuronal cells. However, only a little is known about the downstream effects of NCAM signalling, such as alterations in gene transcription, which are associated with cell fate choice. To examine whether NCAM plays a role in cell fate choice during hippocampal neurogenesis, we performed a gain-of-function study, using a retroviral vector which contained full-length NCAM140 cDNA and the marker gene EGFP, and found that NCAM140 promoted neurogenesis by activating proneural transcription activators with concurrent inhibition of gliogenesis. The enhanced transcript levels of proneural transcription factors in NCAM140-transduced cells were down-regulated by treatment of the cells with mitogen-activated protein kinase kinase (MEK) inhibitor PD098059. Overall, these findings suggest that NCAM140 may facilitate hippocampal neurogenesis via regulation of proneurogenic transcription factors in an extracellular signal-regulated kinase (ERK)-dependent manner.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western / methods
  • Cell Count / methods
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Drug Interactions
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Flavonoids / pharmacology
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology*
  • Hippocampus / embryology
  • Immunohistochemistry / methods
  • Indoles
  • Microtubule-Associated Proteins / metabolism
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neural Cell Adhesion Molecules / physiology*
  • Neurons / metabolism*
  • Neurons / virology
  • Pregnancy
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Retroviridae / genetics*
  • Retroviridae / physiology
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sialic Acids / metabolism
  • Stem Cells / drug effects
  • Stem Cells / physiology*
  • Stem Cells / virology
  • Transduction, Genetic / methods*
  • Tubulin / metabolism

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Indoles
  • MAP2 protein, rat
  • Microtubule-Associated Proteins
  • Neural Cell Adhesion Molecule L1
  • Neural Cell Adhesion Molecules
  • Protein Isoforms
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Sialic Acids
  • Tubulin
  • polysialyl neural cell adhesion molecule
  • Green Fluorescent Proteins
  • DAPI
  • Extracellular Signal-Regulated MAP Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one