Fukutin protein is expressed in neurons of the normal developing human brain but is reduced in Fukuyama-type congenital muscular dystrophy brain.

Fukuyama-type congenital muscular dystrophy (FCMD) results from a mutation in a gene on chromosome 9q31, fukutin, and is characterized pathologically by micropolygyria of the cerebral and cerebellar cortices. To elucidate the physiological function of fukutin as well as its pathological role in FCMD, we raised antisera against fukutin protein and observed its expression in developing human brains with or without FCMD. Western blotting using these antibodies demonstrated a 60-kd band in the fetal but not in postnatal cerebral cortex of the controls. This band appeared negligible in the brains of FCMD fetuses. Immunohistochemistry revealed the localization of fukutin in Cajal-Retzius cells, the subpial granular layer, the neuropil of the marginal zone, the cortical plate neurons, and the ventricular neuroepithelium of the fetal cerebrum. In the fetal cerebellum, fukutin immunoreactivity was localized to the external granule cell layer, molecular layer, Purkinje cells, and some internal granular cells. The immunoreactivity in these structures was reduced markedly in postnatal normal brains, as well as in an FCMD cerebrum at 23 gestational weeks. The spatial and temporal pattern of fukutin expression is compatible with its predicted role: the regulation of neuronal migration in the fetal cerebrum and cerebellum.