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 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.
Xue
Xiao-Jing
XJ
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Yuan
Xiao-Bing
XB
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D064231:Nestin; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011247:Pregnancy; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014746:Vimentin / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D014746:Vimentin; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases