RT Journal Article SR Electronic T1 The protein tyrosine phosphatase Shp2 regulates oligodendrocyte differentiation and early myelination and contributes to timely remyelination. JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 2864-16 DO 10.1523/JNEUROSCI.2864-16.2017 A1 Jared T. Ahrendsen A1 Danielle E. Harlow A1 Lisbet T. Finseth A1 Jennifer N. Bourne A1 Sean P. Hickey A1 Elizabeth A. Gould A1 Cecilia M. Culp A1 Wendy B. Macklin YR 2017 UL http://www.jneurosci.org/content/early/2017/12/07/JNEUROSCI.2864-16.2017.abstract AB Shp2 is a nonreceptor protein tyrosine phosphatase that has been shown to influence neurogenesis, oligodendrogenesis, and oligodendrocyte differentiation. Furthermore, Shp2 is a known regulator of the Akt/mTOR and ERK signaling pathways in multiple cellular contexts, including oligodendrocytes. Its role during later postnatal CNS development or in response to demyelination injury has not been examined. Based on the current studies, we hypothesize that Shp2 is a negative regulator of CNS myelination. Using transgenic mouse technology, we show that Shp2 is involved in oligodendrocyte differentiation and early myelination, but is not necessary for myelin maintenance. We also show that Shp2 regulates the timely differentiation of oligodendrocytes following lysolecithin-induced demyelination, although apparently normal remyelination occurs at a delayed time point. These data suggest that Shp2 is a relevant therapeutic target in demyelinating diseases such as multiple sclerosis.SIGNIFICANCE STATEMENTIn the present study, we show that the protein phosphatase Shp2 is an important mediator of oligodendrocyte differentiation and myelination, both during developmental myelination as well as in myelin regeneration. We provide important insight into the signaling mechanisms regulating myelination and propose that Shp2 acts as a transient brake to the developmental myelination process. Furthermore, we show that Shp2 regulates oligodendrocyte differentiation following demyelination and therefore has important therapeutic implications in diseases such as multiple sclerosis.