Differential Inhibition of Sox10 Functions by Notch-Hes Pathway
In the developing central nervous system, the terminal differentiation of oligodendrocytes (OLs) is regulated by both extrinsic and intrinsic factors. Recent studies have suggested that the Notch-Hes signaling pathway influences the maturation of oligodendrocytes in culture and during development. However, the specific Notch receptors and their downstream effectors Hes genes that are involved in oligodendrocyte maturation have not been investigated systematically. In this study, we showed that Notch1 and Notch3 are expressed in oligodendrocyte precursor cells (OPCs) during gliogenesis, and Hes5 is the major Notch downstream transcription factor that is transiently expressed in OPCs. Overexpression of Notch intracellular domain (NICD) and Hes5 proteins in embryonic chicken spinal cord suppressed both the endogenous and Sox10-induced Mbp gene expression. Unexpectedly, overexpression of NICD/Hes5 did not inhibit Sox10 induction of Olig2 expression and Myrf induced Mbp expression, suggesting the differential inhibitory effects of NICD/Hes5 signaling on Sox10 activation of myelin-related genes and early progenitor genes.
KeywordsOligodendrocytes Hes5 Expression pattern Differentiation
This work was supported by the National Natural Science Foundation of China (Grants 31572224, 31771621) and the Natural Science Foundation of Zhejiang Province (LQ16C090004).
GX and MQ designed the experiments and wrote the manuscript. GX performed the experiments. JD, HW, XG, XX, YZ, XH, KZ, and QZ helped with some experiments. AY and MQ supervised the findings of this work. All authors approved the final paper.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the Laboratory Animal Center, Hangzhou Normal University, and the protocol was approved by the Animal Ethics Committee of Hangzhou Normal University, China.
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