Neuronal expression of the fukutin gene

Fukuyama-type congenital muscular dystrophy (FCMD), a relatively common aut osomal recessive disorder in Japan, is characterized by severe congenital m uscular dystrophy in combination with cortical dysgenesis (polymicrogyria). The gene responsible for FCMD encodes a novel protein, fukutin, which is l ikely to be an extracellular protein, pathological study of brain tissue fr om FCMD fetuses revealed frequent breaks in the glia limitans and basement membrane complex. Disruption of the basal lamina in FCMD muscle was also se en. Thus, structural alteration of the basal lamina appears to play a key r ole in the pathophysiology of FCMD. To investigate the role of fukutin in b rain anomalies, we examined fukutin mRNA expression in the human brain, Nor thern blot and RT-PCR analysis revealed that the fukutin gene is expressed at similar levels in fetal and adult brain, whereas its expression is much reduced in FCMD brains. Tissue in situ hybridization analysis revealed fuku tin mRNA expression in the migrating neurons, including Cajar-Retzius cells and adult cortical neurons, as well as in hippocampal pyramidal cells and cerebellar Purkinje cells. However, we observed no expression in the glia l imitans, the subpial astrocytes (which contribute to basement membrane form ation) or other glial cells. In the FCMD brain, neurons in regions with no dysplasia showed fair expression, whereas transcripts were nearly undetecta ble in the overmigrated dysplastic region. These observations suggest that fukutin function may influence neuronal migration itself rather than format ion of the basement membrane. Furthermore, differences in mRNA levels among neurons in early developmental stages may partially differentiate normal a nd abnormal regions.