Abstract: Studies from nearly 3 decades ago suggested that, in the central nervous system (CNS), myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry (Colello and Schwab, 1994). Over the years, myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth (e.g., MAG, NogoA, OMgp, Semaphorins) (Yiu and He, 2006; Silver et al., 2014). After white matter injury in the adult CNS, myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps, thereby contributing to the inhibition of axonal regrowth. During development, CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them (Foran and Peterson, 1992; Dangata et al., 1996). Therefore, myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring, thereby stabilizing neural circuitry in the CNS (Colello and Schwab, 1994).