Neuronal expression of the fukutin gene.
Fukuyama-type congenital muscular dystrophy (FCMD), a relatively common autosomal recessive disorder in Japan, is characterized by severe congenital muscular dystrophy in combination with cortical dysgenesis (polymicrogyria). The gene responsible for FCMD encodes a novel protein, fukutin, which is likely to be an extracellular protein. Pathological study of brain tissue from FCMD fetuses revealed frequent breaks in the glia limitans and basement membrane complex. Disruption of the basal lamina in FCMD muscle was also seen. Thus, structural alteration of the basal lamina appears to play a key role in the pathophysiology of FCMD. To investigate the role of fukutin in brain anomalies, we examined fukutin mRNA expression in the human brain. Northern 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 fukutin 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 limitans, the subpial astrocytes (which contribute to basement membrane formation) or other glial cells. In the FCMD brain, neurons in regions with no dysplasia showed fair expression, whereas transcripts were nearly undetectable in the overmigrated dysplastic region. These observations suggest that fukutin function may influence neuronal migration itself rather than formation of the basement membrane. Furthermore, differences in mRNA levels among neurons in early developmental stages may partially differentiate normal and abnormal regions.
Sasaki
J
J
Division of Clinical Genetics, Department of Medical Genetics, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2-B9 Yamadaoka, Suita, Osaka 565-0871, Japan.
Ishikawa
K
K
Kobayashi
K
K
Kondo-Iida
E
E
Fukayama
M
M
Mizusawa
H
H
Takashima
S
S
Sakakihara
Y
Y
Nakamura
Y
Y
Toda
T
T
D000328:Adult; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D008565:Membrane Proteins; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C113587:FKTN protein, human; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger