Nestin is essential for mitogen-stimulated proliferation of neural progenitor cells

The intermediate filament (IF) protein nestin is a widely accepted molecular marker for neural progenitor cells (NPCs), but its function during neurogenesis remains largely unknown. We found that in embryonic cortical NPCs down-regulation of the expression of nestin, but not its co-polymer IF protei...

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Bibliographic Details
Published in:Molecular and cellular neuroscience 2010-09, Vol.45 (1), p.26-36
Main Authors: Xue, Xiao-jing, Yuan, Xiao-bing
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Animals
Cell Proliferation
Cells, Cultured
Cerebral Cortex - cytology
Cerebral Cortex - embryology
Female
Intercellular Signaling Peptides and Proteins - metabolism
Intermediate Filament Proteins - genetics
Intermediate Filament Proteins - metabolism
Mitogen-Activated Protein Kinases - genetics
Mitogen-Activated Protein Kinases - metabolism
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nestin
Neural progenitor cells
Neurogenesis - physiology
Neurons - cytology
Neurons - physiology
Phosphatidylinositol 3-Kinases - metabolism
PI3K
Pregnancy
Proliferation
Rats
Rats, Sprague-Dawley
RNA Interference
Signal Transduction - physiology
siRNA
Stem Cells - cytology
Stem Cells - physiology
Vimentin - metabolism
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Summary:The intermediate filament (IF) protein nestin is a widely accepted molecular marker for neural progenitor cells (NPCs), but its function during neurogenesis remains largely unknown. We found that in embryonic cortical NPCs down-regulation of the expression of nestin, but not its co-polymer IF protein vimentin, resulted in a G1 cell-cycle arrest and a severe reduction in the generation of neurons. Furthermore, down-regulating nestin expression in cultured cortical NPCs markedly suppressed their colony-formation ability and blocked the elevation of the cyclin D1/E protein level in response to the treatment with bFGF. Interestingly, nestin down-regulation caused a marked suppression in the activation of the phosphoinositide 3-kinase (PI3K) pathway but not the mitogen-activated protein kinase (MAPK) pathway in these NPCs. Moreover, defects in the proliferation of cortical NPCs caused by nestin down-regulation could be prevented by up-regulating PI3K activity. Thus, nestin is essential for the proliferation of NPCs by promoting the activation of PI3K in response to mitogenic growth factors.
ISSN:1044-7431
1095-9327
DOI:10.1016/j.mcn.2010.05.006