Exp Mol Med.  2006 Dec;38(6):732-738.

Neural cell adhesion molecule (NCAM) induces neuronal phenotype acquisition in dominant negative MEK1-expressing hippocampal neural progenitor cells

• Kim BW
• Son H

Abstract

It has been shown that neural cell adhesion molecule (NCAM)-induced neuronal differentiation is extracellular signal-regulated kinase (ERK)-dependent. However, an involvement of the mitogen activated protein kinase (MAPK) kinase (MEK), an upstream kinase of ERK, has not been directly demonstrated in this process. Therefore, we investigated whether the MEK1 plays a critical role in the NCAM-induced neuronal differentiation of hippocampal neural progenitor cells (NPCs). NPCs were transiently transfected with expression plasmids encoding activated or dominant negative (DN) forms of MEK1. The expression of DN MEK1 inhibited neuronal phenotype acquisition and soluble NCAM rescued the defect in the neuronal phenotype acquisition in DN-MEK1-transfected cells, suggesting that NCAM might contribute to the neuronal differentiation via distinct, parallel pathways including the MEK pathway. In cells expressing wild type MEK1 or constitutively active MEK1 on the other hand, the percentage of cells positive for beta-tubulin type III (Tuj1), a marker for early postmitotic neurons, was higher than seen in vector-transfected cells. These results suggest that the activation of MEK1 is required for obtaining neuronal phenotype in NPCs.

Keyword

hippocampus; MAP kinase kinase 1; neural cell adhesion molecules; rats

MeSH Terms

Transfection
Stem Cells/cytology/drug effects/*metabolism
Solubility
Rats
*Phenotype
Neurons/cytology/drug effects/*metabolism
Neural Cell Adhesion Molecules/*pharmacology
Mutation/genetics
MAP Kinase Kinase 1/genetics/*metabolism
Hippocampus/cytology/drug effects/*metabolism
Gene Expression Regulation
Cells, Cultured
Cell Differentiation
Animals