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The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for(More)
After central nervous system (CNS) demyelination-such as occurs during multiple sclerosis-there is often spontaneous regeneration of myelin sheaths, mainly by oligodendrocytes but also by Schwann cells. The origins of the remyelinating cells have not previously been established. We have used Cre-lox fate mapping in transgenic mice to show that(More)
Demyelination in the adult CNS can be followed by extensive repair. However, in multiple sclerosis, the differentiation of oligodendrocyte lineage cells present in demyelinated lesions is often inhibited by unknown factors. In this study, we test whether myelin debris, a feature of demyelinated lesions and an in vitro inhibitor of oligodendrocyte precursor(More)
Olig1 and Olig2 are closely related basic helix-loop-helix (bHLH) transcription factors that are expressed in myelinating oligodendrocytes and their progenitor cells in the developing central nervous system (CNS). Olig2 is necessary for the specification of oligodendrocytes, but the biological functions of Olig1 during oligodendrocyte lineage development(More)
The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. We generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts that encode the retinoid acid receptor RXR-γ were differentially expressed during(More)
Remyelination following central nervous system demyelination is essential to prevent axon degeneration. However, remyelination ultimately fails in demyelinating diseases such as multiple sclerosis. This failure of remyelination is likely mediated by many factors, including changes in the extracellular signalling environment. Here, we examined the expression(More)
Within the adult CNS, a quiescent population of oligodendrocyte progenitor cells (OPCs) become activated in response to demyelination and give rise to remyelinating oligodendrocytes. During development, OPC differentiation is controlled by several transcription factors including Olig1 and Olig2, and Nkx2.2. We hypothesized that these genes may serve similar(More)
Although macrophages are mediators of CNS demyelination, they are also implicated in remyelination. To examine the role of macrophages in CNS remyelination, adult rats were depleted of monocytes using clodronate liposomes and demyelination induced in the spinal cord white matter using lysolecithin. In situ hybridization for scavenger receptor-B and myelin(More)
Several randomized trials have demonstrated non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations can achieve favorable clinical outcomes on treatment with EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation is considered as a predictive marker for efficacy of EGFR-TKIs in NSCLC. Here we show(More)
Permanent damage to white matter tracts, comprising axons and myelinating oligodendrocytes, is an important component of brain injuries of the newborn that cause cerebral palsy and cognitive disabilities, as well as multiple sclerosis in adults. However, regulatory factors relevant in human developmental myelin disorders and in myelin regeneration are(More)