Laminin regulates oligodendrocyte development and myelination

AbstractOligodendrocytes are the cells that myelinate axons and provide trophic support to neurons in the CNS. Their dysfunction has been associated with a group of disorders known as demyelinating diseases, such as multiple sclerosis. Oligodendrocytes are derived from oligodendrocyte precursor cells, which differentiate into premyelinating oligodendrocytes and eventually mature oligodendrocytes. The development and function of oligodendrocytes are tightly regulated by a variety of molecules, including laminin, a major protein of the extracellular matrix. Accumulating evidence suggests that laminin actively regulates every aspect of oligodendrocyte biology, including survival, migration, proliferation, differentiation, and myelination. How can laminin exert such diverse functions in oligodendrocytes? It is speculated that the distinct laminin isoforms, laminin receptors, and/or key signaling molecules expressed in oligodendrocytes at different developmental stages are the reasons. Understanding molecular targets and signaling pathways unique to each aspect of oligodendrocyte biology will enable more accurate manipulation of oligodendrocyte development and function, which may have implications in the therapies of demyelinating diseases. Here in this review, we first introduce oligodendrocyte biology, followed by the expression of laminin and laminin receptors in oligodendrocytes and other CNS cells. Next, the functions of laminin in oligodendrocyte biology, including survival, migration, proliferation, differentiation, and myelination, are discussed in detail. Last, key questions and challenges in the field are discussed. By providing a comprehensive review on laminin's roles in OL lineage cells, we hope to stimulate novel hypotheses and encourage new research in the field.