Neurotrophic Factor‐α1: A Key Wnt‐β‐Catenin Dependent Anti‐Proliferation Factor and ERK‐Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment
MetadataShow full item record
AbstractEmbryonic neurodevelopment involves inhibition of proliferation of multipotent neural stem cells (NSCs) followed by differentiation into neurons, astrocytes and oligodendrocytes to form the brain. We have identified a new neurotrophic factor, NF‐α1, which inhibits proliferation and promotes differentiation of NSC/progenitors derived from E13.5 mouse cortex. Inhibition of proliferation of these cells was mediated through negatively regulating the Wnt pathway and decreasing β‐catenin. NF‐α1 induced differentiation of NSCs to astrocytes by enhancing Glial Fibrillary Acidic Protein (GFAP) expression through activating the ERK1/2‐Sox9 signaling pathway. Cultured E13.5 cortical stem cells from NF‐α1‐knockout mice showed decreased astrocyte numbers compared to wild‐type mice, which was rescued by treatment with NF‐α1. In vivo, immunocytochemistry of brain sections and Western blot analysis of neocortex of mice showed a gradual increase of NF‐α1 expression from E14.5 to P1 and a surge of GFAP expression at P1, the time of increase in astrogenesis. Importantly, NF‐α1‐Knockout mice showed ∼49% fewer GFAP positive astrocytes in the neocortex compared to WT mice at P1. Thus, NF‐α1 is critical for regulating antiproliferation and cell fate determination, through differentiating embryonic stem cells to GFAP‐positive astrocytes for normal neurodevelopment. Stem Cells 2017;35:557–571. Copyright 2016 AlphaMed Press
SponsorsThis research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, USA.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85002141995&doi=10.1002%2fstem.2511&partnerID=40&md5=a467b73bd4330c2c51dbe53a3a7d2a02; http://hdl.handle.net/10713/10045
- Toxoplasma gondii inhibits differentiation of C17.2 neural stem cells through Wnt/β-catenin signaling pathway.
- Authors: Gan X, Zhang X, Cheng Z, Chen L, Ding X, Du J, Cai Y, Luo Q, Shen J, Wang Y, Yu L
- Issue date: 2016 Apr 22
- PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes.
- Authors: Choi I, Choi DJ, Yang H, Woo JH, Chang MY, Kim JY, Sun W, Park SM, Jou I, Lee SH, Joe EH
- Issue date: 2016 Jan 8
- Sevoflurane affects neurogenesis through cell cycle arrest via inhibiting wnt/β-catenin signaling pathway in mouse neural stem cells.
- Authors: Liu S, Fang F, Song R, Gao X, Jiang M, Cang J
- Issue date: 2018 Sep 15
- Cloning, gene regulation, and neuronal proliferation functions of novel N-terminal-truncated carboxypeptidase E/neurotrophic factor-αl variants in embryonic mouse brain.
- Authors: Xiao L, Yang X, Sharma VK, Loh YP
- Issue date: 2019 Jan
- [Differentiation of induced pluripotent stem cells into neural stem cells induced by brain-derived neurotrophic factor via Wnt/β-catenin and extracellular signal-regulated kinase/mitogen-activated protein kinases signal pathway].
- Authors: Chen SQ, Huang M, Liu CL, Shen YY, Cai Q, Wang PJ
- Issue date: 2017 Nov 7