Co-localization of fukutin and alpha-dystroglycan in the mouse central nervous system.

Hypoglycosylation of alpha-dystroglycan (alpha-DG) has been identified in several human diseases associated with muscular dystrophy and brain malformations, including Fukuyama-type congenital muscular dystrophy (FCMD) caused by mutations in the fukutin gene. Although disruption of the intra-extra membrane linkage in the sarcolemma via the dystroglycan (DG) has been hypothesized as a possible underlying mechanism, little is known about the pathogenesis of brain anomalies in these conditions. In this study, we examined the patterns of expression of fukutin and alpha-DG in developing and adult mouse brains. Antisera against fukutin and alpha-DG identified neurons of the fetal cerebral and cerebellar cortex and the subpial pontine migratory stream. In adult mice, fukutin and alpha-DG were extensively co-expressed in neurons of the cerebral and cerebellar cortex, hippocampus, basal ganglia and olfactory bulb, as well as in the pontine nucleus and the cranial nerve nuclei. These results support the hypothesis that fukutin is involved in the glycosylation process of alpha-DG and that a defect in this process plays an essential role in the pathogenesis of FCMD. Further research into the physiological function of alpha-DG in migrating and mature neurons is required.