Immunohistochemical expression of doublecortin in the human cerebrum: comparison of normal development and neuronal migration disorders.
Immunohistochemical expression of the doublecortin (DCX) gene product was investigated in cerebral cortices from 33 normal developing human, aged 9 gestational weeks (GW) to 29 years, and from 26 patients with various neuronal migration disorders, aged 19 GW to 34 years. DCX immunoreactivity was detected predominantly in the fetal cerebral cortex. The neurons in the cortical plate (CP) exhibited positive labeling at 9 GW. Staining was the most marked intense at 12-20 GW, and gradually decreased thereafter, only relatively weak immunoreactivity remaining in pyramidal cells. Comparison of the immunohistochemical characteristics of DCX and those of nestin and vimentin indicated the early expression of DCX in neuroepithelial stem cells of the subventricular germinal layer, as well as in neurons of the CP. The most marked intense expression in the period of neuronal migration strongly indicated its role in neuronal migration. The abnormal distribution of DCX immunolabeling in the cerebral cortex was associated with a neuronal disarrangement in some migration disorders, such as Miller-Dieker syndrome and Fukuyama congenital muscular dystrophy. Decreased DCX immunolabeling was demonstrated in fetuses and infants with Zellweger syndrome, implicating DCX in the neuronal migration abnormality in this syndrome.
Qin
J
J
Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
Mizuguchi
M
M
Itoh
M
M
Takashima
S
S
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001921:Brain / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009421:Nervous System Malformations / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D064231:Nestin; D009474:Neurons / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism*; D011247:Pregnancy; D014746:Vimentin / Q000378:metabolism
C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D009479:Neuropeptides; D014746:Vimentin