Dystroglycan, a membrane receptor linking the extracellular matrix to the inner cell cytoskeleton, is predicted to regulate the formation of myelin sheath in the Central Nervous System (CNS). Myelin sheaths are produced by oligodendrocytes in a cellular process called “myelination” in which the specialized membrane of oligodendrocyte processes wraps multiple times around the axons of neurons. In the CNS, impulse transmission is drastically enhanced in neurons with myelinated axons, and dysregulation of myelination contributes to several complex disorders (i.e. Muscular Dystrophies, Multiple Sclerosis, Cerebral Palsy).
While the mechanisms underlying myelination continue to be discovered, based on work using cultured oligodendrocytes we hypothesized that dystroglycan might be an important receptor that regulates myelin. In our current study, brain lysates were isolated from transgenic mice engineered to lack dystroglycan solely in oligodendrocytes and compared to wild type mice at postnatal day 21 (a period when myelination in the cerebral cortex is at its peak). Protein lysates prepared from various CNS regions known to undergo high levels of myelination (i.e. Cerebral Cortex, Cerebellum, and Spinal Cord) were evaluated by western blotting.
Level of Myelin Basic Protein (MBP), a key component of myelin, were compared between wild type and dystroglycan mutant brain regions. Our preliminary findings suggest that dystroglycan delays myelination, with brain regions that lack dystroglycan having increased levels of MBP. Ongoing studies will ultimately enable us to more fully determine the role of dystroglycan in regulating CNS myelination.