Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination
- Zhejiang University School of Medicine, China
- Zhejiang University City College, China
- Hangzhou Normal University, China
Abstract
Oligodendrocytes (OLs) myelinate axons and provide electrical insulation and trophic support for neurons in the central nervous system (CNS). Platelet-derived growth factor (PDGF) is critical for steady-state number and differentiation of oligodendrocyte precursor cells (OPCs), but its downstream targets are unclear. Here, we show for the first time that Gab1, an adaptor protein of receptor tyrosine kinase, is specifically expressed in OL lineage cells and is an essential effector of PDGF signaling in OPCs in mice. Gab1 is down-regulated by PDGF stimulation and up-regulated during OPC differentiation. Conditional deletions of Gab1 in OLs cause CNS hypomyelination by affecting OPC differentiation. Moreover, Gab1 binds to downstream GSK3β and regulated its activity, and thereby affects the nuclear accumulation of β-catenin and the expression of a number of transcription factors critical to myelination. Our work uncovers a novel downstream target of PDGF signaling, which is essential to OPC differentiation and CNS myelination.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Ministry of Science and Technology of the People's Republic of China (2017YFA0104200)
- Ying Shen
National Natural Science Foundation of China (31571051)
- Liang Zhou
National Natural Science Foundation of China (81625006)
- Ying Shen
National Natural Science Foundation of China (31820103005)
- Ying Shen
Natural Science Foundation of Zhejiang Province (Z15C090001)
- Ying Shen
Natural Science Foundation of Zhejiang Province (LQ17C090001)
- Na Wang
Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT31038)
- Ying Shen
Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT31041)
- Ying Shen
Chinese Ministry of Education Project 111 Program (B13026)
- Ying Shen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All of the animals were handled according to approved protocol (ZJU20160019) of the Animal Experimentation Ethics Committee of Zhejiang University.
Copyright
© 2020, Zhou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination
eLife 9:e52056.
https://doi.org/10.7554/eLife.52056
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