期刊
GENES & DEVELOPMENT
卷 29, 期 16, 页码 1677-1682出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.261677.115
关键词
neurofibromin; neuroglial progenitor; AKT; MEK; Jagged1; Notch; astrocyte
资金
- American Brain Tumor Association
- Emily Dorfman Foundation
- National Institutes of Health [R01-NS065547-01]
Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disordercaused byimpaired function of the neurofibromin RAS regulator. Using a combination of Nf1 genetically engineered mice and pharmacological/genetic inhibition approaches, wereport that neurofibromin differentially controls neural stem cell (NSC) proliferation and multilineage differentiation through the selective use of the PI3K/AKT and RAF/MEK pathways. While PI3K/AKT governs neurofibromin-regulated NSC proliferation, multilineage differentiationis MEK-dependent. Moreover, whereas MEK-regulated multilineage differentiation requires Smad3-induced Jagged-1 expression and Notch activation, MEK/Smad3-regulated Hes1 induction is only responsible for astrocyte and neuronal differentiation. Collectively, these findings establish distinct roles for the RAS effector pathways in regulating brain NSC function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据