Progression through the oligodendrocyte lineage is mediated by numerous factors. As highlighted, signaling from the extracellular matrix (sub-figure adapted from Bauer et al., 2009) is critical in modulating the dynamic cytoskeletal reorganization of the premyelinating-myelinating oligodendrocyte transition. Additionally, signal transduction through the Akt/mTOR pathway, modified by PTEN, has been shown to be a regulator of myelin biogenesis. It should be noted that the ERK1/2 signaling pathway is also involved in regulating CNS myelination (Ishii et al., 2012), but this figure focuses on the Akt/mTOR pathway investigated in Snaidero et al. (2014).