Signaling pathways of the early differentiation of neural stem cells by neurotrophin-3.
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.
Lim
Myung-Shin
MS
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Kwanak-gu, Seoul 151-742, Republic of Korea.
Nam
Sang-Hyun
SH
Kim
Sun-Jung
SJ
Kang
Seog-Youn
SY
Lee
Yong-Soon
YS
Kang
Kyung-Sun
KS
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000008:administration & dosage*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
D020933:Neurotrophin 3