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Erk1/2 but not PI3K pathway is required for neurotrophin 3-induced oligodendrocyte differentiation of post-natal neural stem cells.
J Neurochem. 2004 Sep; 90(6):1339-47.JN

Abstract

Neurotrophin 3 (NT3) induces mouse cortical stem cells to an asymmetric division from a symmetric division, suggesting that NT3 may work as an early differentiative signal for neural stem cells (NSCs). Here, using cultured post-natal hippocampal stem cells as a model, we demonstrated that NT3-stimulation causes NSCs to differentiate into oligodendrocyte precursors (OLPs) through an extracellular signal-related kinase1/2 (Erk1/2)-dependent pathway. Following the treatment of NT3 for 24 h, NSCs differentiated into more OLPs and fewer neurons, whereas the proliferation and survival of OLPs were not affected. NT3 induced a series of intracellular responses including enhancement of phosphorylation of Erk1/2 or Akt and increase of expression of oligodendrocyte lineage gene (Olig)-1, a transcriptional factor known to participate in oligodendrocyte development. Application of U0126, a specific inhibitor of MEK1/2 which are upstream to Erk1/2, blocked the phosphorylation of Erk1/2, suppressed the expression of Olig-1 and prevented NSC differentiation into OLPs in response to NT3 stimulation. Blockade of TrkC also inhibited the differentiation of NSCs to OLPs induced by NT3. However, administration of LY294002, an inhibitor of phosphatidylinositol 3 kinase (PI3K), blocked the phosphorylation of Akt but did not affect the effect of NT3 on the expression of Olig-1 and on NSC differentiation into OLPs. Taken together, these results suggest that NT3 induce NSCs to differentiate into OLPs by enhancing the expression of Olig-1 through an Erk1/2-dependent pathway.

Authors+Show Affiliations

Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15341518

Citation

Hu, Xinhua, et al. "Erk1/2 but Not PI3K Pathway Is Required for Neurotrophin 3-induced Oligodendrocyte Differentiation of Post-natal Neural Stem Cells." Journal of Neurochemistry, vol. 90, no. 6, 2004, pp. 1339-47.
Hu X, Jin L, Feng L. Erk1/2 but not PI3K pathway is required for neurotrophin 3-induced oligodendrocyte differentiation of post-natal neural stem cells. J Neurochem. 2004;90(6):1339-47.
Hu, X., Jin, L., & Feng, L. (2004). Erk1/2 but not PI3K pathway is required for neurotrophin 3-induced oligodendrocyte differentiation of post-natal neural stem cells. Journal of Neurochemistry, 90(6), 1339-47.
Hu X, Jin L, Feng L. Erk1/2 but Not PI3K Pathway Is Required for Neurotrophin 3-induced Oligodendrocyte Differentiation of Post-natal Neural Stem Cells. J Neurochem. 2004;90(6):1339-47. PubMed PMID: 15341518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erk1/2 but not PI3K pathway is required for neurotrophin 3-induced oligodendrocyte differentiation of post-natal neural stem cells. AU - Hu,Xinhua, AU - Jin,Lu, AU - Feng,Linyin, PY - 2004/9/3/pubmed PY - 2004/10/28/medline PY - 2004/9/3/entrez SP - 1339 EP - 47 JF - Journal of neurochemistry JO - J. Neurochem. VL - 90 IS - 6 N2 - Neurotrophin 3 (NT3) induces mouse cortical stem cells to an asymmetric division from a symmetric division, suggesting that NT3 may work as an early differentiative signal for neural stem cells (NSCs). Here, using cultured post-natal hippocampal stem cells as a model, we demonstrated that NT3-stimulation causes NSCs to differentiate into oligodendrocyte precursors (OLPs) through an extracellular signal-related kinase1/2 (Erk1/2)-dependent pathway. Following the treatment of NT3 for 24 h, NSCs differentiated into more OLPs and fewer neurons, whereas the proliferation and survival of OLPs were not affected. NT3 induced a series of intracellular responses including enhancement of phosphorylation of Erk1/2 or Akt and increase of expression of oligodendrocyte lineage gene (Olig)-1, a transcriptional factor known to participate in oligodendrocyte development. Application of U0126, a specific inhibitor of MEK1/2 which are upstream to Erk1/2, blocked the phosphorylation of Erk1/2, suppressed the expression of Olig-1 and prevented NSC differentiation into OLPs in response to NT3 stimulation. Blockade of TrkC also inhibited the differentiation of NSCs to OLPs induced by NT3. However, administration of LY294002, an inhibitor of phosphatidylinositol 3 kinase (PI3K), blocked the phosphorylation of Akt but did not affect the effect of NT3 on the expression of Olig-1 and on NSC differentiation into OLPs. Taken together, these results suggest that NT3 induce NSCs to differentiate into OLPs by enhancing the expression of Olig-1 through an Erk1/2-dependent pathway. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/15341518/Erk1/2_but_not_PI3K_pathway_is_required_for_neurotrophin_3_induced_oligodendrocyte_differentiation_of_post_natal_neural_stem_cells_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=2004&volume=90&issue=6&spage=1339 DB - PRIME DP - Unbound Medicine ER -