Differential Inhibition of Sox10 Functions by Notch-Hes Pathway

Abstract

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.