Our research focuses on myelin biogenesis in health and disease, particular dedicated to multiple sclerosis (MS) and on topics related to trafficking and signalling in oligodendrocytes. We have identified the polarized nature of oligodendrocytes, in which cognate apical-like and basolateral-like trafficking routes operate to plasma membrane of the cell body and myelin membrane, respectively. Another aspect of our work aims at revealing environmental restrictions in MS lesions that underlie remyelination failure. We focuses on extracellular signals, which are involved in oligodendrocyte development and myelination. We particularly investigate the role of neuronal factors and the relevance of various ECM constituents and their signaling pathways in remyelination We have identified environmental signaling abnormalities in MS lesions, such as fibronectin aggregates and the persistent presence of neuronal galectin-4, that hamper remyelination. Currently we aim to device strategies that reverse signal malfunctioning of fibronectin aggregates and galectin-4 so as to favor the development of therapeutics to promote endogenous remyelination and/or overcome remyelination failure in MS lesions, thereby halting disease progression.