Signaling pathways of the early differentiation of neural stem cells by neurotrophin-3 |
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Authors: | Lim Myung-Shin Nam Sang-Hyun Kim Sun-Jung Kang Seog-Youn Lee Yong-Soon Kang Kyung-Sun |
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Affiliation: | Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Kwanak-gu, Seoul 151-742, Republic of Korea. |
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Abstract: | Neurotrophin-3 (NT-3) is well known to play an important role in facilitating neuronal survival and differentiation during development. However, the mechanisms by which neurotrophin-3 promotes prolonged Akt/MAPK signaling at an early stage are not well understood. Here, we report that NT-3 works at an early stage of neuronal differentiation in mouse neural stem cells (NSCs). After treatment with NT-3 for 12h, more NSCs differentiated into neurons than did untreated cells. These findings demonstrated that stimulation with NT-3 causes NSCs to differentiate into neurons through a phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and the phosphorylated extracellular signal-regulated kinase (ERK) pathway. In addition, treatment with NT-3 induced neurite outgrowth by specific phosphorylation of p38 MAPK, which was accompanied by neuronal differentiation. Taken together, these results suggest that NT-3, along with the Trk C receptors in NSCs, might lead to the survival and neuronal differentiation of NSCs via two distinct downstream signaling pathways at an early stage of neuronal differentiation. |
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Keywords: | Neural stem cells Neurotrophin-3 Neuronal differentiation Neurite outgrowth Akt ERK p38 |
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