Fibroblast growth factor receptor signaling in oligodendrocytes regulates myelin sheath thickness.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Miki FurushoRashmi Bansal

Abstract

Formation of the CNS white matter is developmentally tightly regulated, but the molecules and mechanisms of myelination control in the postnatal CNS are poorly understood. Here, we show that myelin growth is controlled by fibroblast growth factor (FGF) signaling, originally identified as a proliferative signal for oligodendrocyte precursor cells (OPCs) in vitro. We created two lines of mice lacking both FGF receptor 1 (Fgfr1) and Fgfr2 in oligodendrocyte-lineage cells but found that in these mice OPC proliferation and differentiation were unaffected. In addition, axonal ensheathment and the initiation of myelination were on time. However, the rapid growth of CNS myelin, normally occurring in the second postnatal week, was strongly inhibited. Throughout adulthood, the myelin sheath remained disproportionately thin relative to the axon caliber. In adult mice, mutant oligodendrocytes were normal in number, whereas the transcription of major myelin genes was reduced. This FGF receptor-mediated stimulation of mature oligodendrocytes could also be modeled in vitro, demonstrating that enhanced expansion of oligodendroglial processes requires signaling by extracellular signal regulated kinase-1 and -2 (Erk1/2), downstream mediators of ...Continue Reading

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