Stage-dependent regulation of oligodendrocyte development and enhancement of myelin repair by dominant negative Master-mind 1 protein.

摘要: Notch signaling has been implicated in the inhibition of oligodendrocyte differentiation and myelin gene expression during early development. However, inactivation a particular or Hes only produces mild phenotype development possibly due to functional redundancies among closely related family members. To uncover full role regeneration, we generated Sox10rtTA/+ ; TetO-dnMAML1 double transgenic mice which dominant negative Master-mind 1 (dnMAML1) can be selectively induced precursor cells (OPCs) for complete blockade signaling. It is found that dnMAML1 leads robust precocious OL premature axonal myelination spinal cord, by upregulating Nkx2.2 downregulating Pdgfra expression. Unexpectedly, at late embryonic stages, dramatically increased number OPCs, indicating stage-dependent effect on OPC proliferation. In addition, also significantly enhances remyelination following chemical-induced demyelination, providing promising therapeutic target lesion repair demyelinating disease.