Erk1/2 but not PI3K pathway is required for neurotrophin 3-induced oligodendrocyte differentiation of post-natal neural stem cells

Journal of Neurochemistry
Xinhua HuLinyin Feng

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 phosphatid...Continue Reading

Citations

May 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ki-Chul HwangDong-Wook Kim
May 19, 2006·The European Journal of Neuroscience·Anders I PerssonPeter S Eriksson
Mar 7, 2012·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kenji WatataniYukiko Gotoh
Jan 5, 2011·Neuroscience Letters·Haoming LiLinqing Zou
Dec 23, 2014·Translational Neuroscience·Kate Marie Lewis, Claudia Petritsch
Apr 30, 2014·Molecular Neurobiology·Honghua YuanXiaorong Zhu
Dec 19, 2019·Frontiers in Neuroscience·Anna O'SullivanSebastien Couillard-Despres

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