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 3q31, 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 cer ebral cortex of the controls. This band appeared negligible in the brains o f FCMD fetuses. Immunohistochemistry revealed the localization of fukutin i n Cajal-Retzius cells, the subpial granular layer, the neuropil of the marg inal zone, the cortical plate neurons, and the ventricular neuroepithelium of the fetal cerebrum. In the fetal cerebellum, fukutin immunoreactivity wa s localized to the external granule cell layer, molecular layer, Purkinje c ells, and some internal granular cells. The immunoreactivity in these struc tures was reduced markedly in postnatal normal brains, as well as in an FCM D cerebrum at 23 gestational weeks. The spatial and temporal pattern of fuk utin expression is compatible with its predicted role: the regulation of ne uronal migration in the fetal cerebrum and cerebellum.