The role of beta1 integrin in myelination and remyelination

Myelination is a process of cellular specialization, where oligodendrocytes in the central nervous system (CNS) undergo maturation to form the myelin sheath. Proper formation of the myelin sheath is an important process as it is responsible for rapid saltatory conduction along nerves and is required for the survival of the axons. Multiple Sclerosis (MS) is a disease that can be characterized by the degeneration of the myelin sheath within the CNS and the inability of the myelin sheath to reform. The damage or loss of myelin results in the disruption of impulses along nerve axons and ultimately leads to neurological symptoms. Therefore, it is critical to determine how oligodendrocytes develop and myelinate axons, and it is important we learn how to use this information to repair the lost or damaged myelin. Research is advancing our understanding of the various factors involved in oligodendrocyte development. In particular, much research has shown the importance of beta1 integrin in oligodendrocyte biology and in myelin membrane formation.Further analysis of the dominant-negative mouse model permitted us to get a better understanding of the role of beta1 integrin in oligodendrocyte development during remyelination. Our work demonstrates that beta1 integrin is important in the survival of oligodendrocytes acting primarily through the MAPK signaling pathway.Through the use of the dominant-negative beta1 integrin mouse model, we demonstrated in vivo the importance of beta1 integrin in myelination and remyelination, we furthered our understanding of beta1 integrin's role in the survival of oligodendrocyte development, and lastly we determined downstream signaling pathways that may contribute to the function of beta1 integrin in myelination and remyelination.We are the first to demonstrate in vivo that beta1 integrin is important in myelination and remyelination. With the use of the proteolipid protein promoter (PLP), we generated a transgenic mouse model that expresses the beta1 integrin subunit minus the cytoplasmic domain. This dominant-negative beta1 integrin mouse model is characterized by myelin defects in the optic nerve and spinal cord. Under the cuprizone-induced demyelination/remyelination model, the dominant-negative beta1 integrin mouse has delayed or impaired remyelination. We also show that the mitogen-activated protein kinase (MAPK) pathway appears to be important in beta1 integrin signaling during myelination and remyelination.