Erk1/2 promotes proliferation and inhibits neuronal differentiation of neural stem cells.
Neural stem cells (NSCs) are in a complex niche in which cell-extrinsic cues and cell-intrinsic genetic mechanisms in chorus mediate their cellular processes such as self-renewal and differentiation. In this study, we found that inactivation of Erk1/2 with U0126 in NSCs significantly promoted neuronal differentiation and inhibited proliferation. Sustained Erk1/2 inactivity was required in this process. We also found that nerve growth factor (NGF) and collagen could promote the proliferation and inhibit neuronal differentiation by activating phosphorylation of Erk1/2. Cell-cycle regulators such as cyclin-dependent kinase 2 (Cdk2), Cyclin D1 and Hes1 mediated the effect of Erk on NSCs proliferation and differentiation. Our results showed that Erk1/2 played an important role in the interplay between cell-extrinsic cues and cell-intrinsic genetic mechanisms in neural stem cell biology.
Wang
Bin
B
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China.
Gao
Yuan
Y
Xiao
Zhifeng
Z
Chen
Bing
B
Han
Jin
J
Zhang
Jing
J
Wang
Xia
X
Dai
Jianwu
J
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation; D003094:Collagen / Q000494:pharmacology; D019938:Cyclin D1 / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2 / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D004815:Epidermal Growth Factor / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D066298:In Vitro Techniques; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D002070:Butadienes; D003094:Collagen; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D004815:Epidermal Growth Factor; D016222:Fibroblast Growth Factor 2; D018398:Homeodomain Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020932:Nerve Growth Factor; D009570:Nitriles; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C113580:U 0126