Individual Oligodendrocytes Have Only a Few Hours in which to Generate New Myelin Sheaths In Vivo

The number of myelin sheaths made by individual oligodendrocytes regulates the extent of myelination, which profoundly affects central nervous system function. It remains unknown when, during their life, individual oligodendrocytes can regulate myelin sheath number in vivo. We show, using live imaging in zebrafish, that oligodendrocytes make new myelin sheaths during a period of just 5 hr, with regulation of sheath number after this time limited to occasional retractions. We also show that activation and reduction of Fyn kinase in oligodendrocytes increases and decreases sheath number per cell, respectively. Interestingly, these oligodendrocytes also generate their new myelin sheaths within the same period, despite having vastly different extents of myelination. Our data demonstrate a restricted time window relative to the lifetime of the individual oligodendrocyte, during which myelin sheath formation occurs and the number of sheaths is determined. [Display omitted] •Time-lapse imaging of myelin sheath formation by oligodendrocytes (OLs) in vivo•Individual OLs initiate formation of new myelin sheaths in a short 5 hr period•OLs remove a small number of myelin sheaths within 2 days of initiating myelination•Fyn kinase regulates myelin sheath number per OL, also within a short 5 hr period How do individual oligodendrocytes contribute to ongoing CNS myelination throughout life? Using live imaging in zebrafish, Czopka et al. find that individual newborn oligodendrocytes have a period of about 5 hr in which to generate their myelin sheaths, indicating a restricted ability to contribute to lifelong regulation of global myelination.