The guanine nucleotide exchange factor Vav3 modulates oligodendrocyte precursor differentiation and supports remyelination in white matter lesions

Main Points Vav3−/− oligodendrocytes (OLs) show accelerated maturation Vav3−/− OLs posses impaired myelination and remyelination potency in vitro Vav3−/− mice display reduced remyelination in vivo Vav3−/− OLs present changed activation levels of Rho GTPases AbstractThe tightly controlled processes of myelination and remyelination require the participation of the cytoskeleton. The reorganization of the cytoskeleton is controlled by small GTPases of the RhoA family. Here, we report that Vav3, a Rho GTPase regulating guanine nucleotide exchange factor (GEF) is involved in oligodendrocyte maturation, myelination and remyelination. When Vav3 was eliminated by genetic recombination, oligodendrocyte precursor cell (OPC) differentiation toward mature oligodendrocytes was accelerated. In contrast, Vav3 ‐deficient oligodendrocytes displayed a reduced capacity to myelinate synthetic microfibers in vitro. Furthermore, remyelination was impaired in Vav3 knockout cerebellar slice cultures that were demyelinated by the addition of lysolecithin. In agreement with these observations, remyelination was c ompromised when the cuprizone model of myelin lesion was performed in Vav3‐deficient mice. When Vav3‐deficient oligodendrocytes were examined with Förster resonance energy transfer (FRET)‐based biosensors, an altered activation profile of RhoA GTPases was revealed on the cellular level, which could be responsible for an impaired remyelination. Taken together, this stud...
Source: Glia - Category: Neurology Authors: Tags: RESEARCH ARTICLE Source Type: research