Aberrant neuronal-glial differentiation in Taylor-type focal cortical dysplasia (type IIA/B).
Focal cortical dysplasia (FCD) type IIA/B (Taylor type) is a malformation of cortical development characterized by laminar disorganization and dysplastic neurons. FCD IIA and FCD IIB denote subtypes in which balloon cells are absent or present, respectively. The etiology of FCD IIA/B is unknown, but previous studies suggest that its pathogenesis may involve aberrant, mixed neuronal-glial differentiation. To investigate whether aberrant differentiation is a consistent phenotype in FCD IIA/B, we studied a panel of neuronal and glial marker antigens in a series of 15 FCD IIB cases, and 2 FCD IIA cases. Double-labeling immunofluorescence and confocal imaging revealed that different combinations of neuronal and glial antigens were co-expressed by individual cells in all cases of FCD IIA/B, but not in control cases of epilepsy due to other causes. Co-expression of neuronal and glial markers was most common in balloon cells, but was also observed in dysplastic neurons. The relative expression of neuronal and glial antigens varied over a broad range. Microtubule-associated protein 1B, an immature neuronal marker, was more frequently co-expressed with glial antigens than were mature neuronal markers, such as neuronal nuclear antigen. Our results indicate that aberrant neuronal-glial differentiation is a consistent and robust phenotype in FCD IIA/B, and support the hypothesis that developmental defects of neuronal and glial fate specification play an important role in its pathogenesis.
Englund
Chris
C
Department of Pathology, Box 359791, Harborview Medical Center, University of Washington School of Medicine, 325 Ninth Ave., Seattle, WA 98104, USA.
Folkerth
Rebecca D
RD
Born
Donald
D
Lacy
J Matthew
JM
Hevner
Robert F
RF
D000293:Adolescent; D000328:Adult; D000368:Aged; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009421:Nervous System Malformations / Q000378:metabolism / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods
D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D009418:S100 Proteins; C085284:microtubule-associated protein 1B; C051774:neurofilament protein H; C007293:DAPI; D010751:Phosphopyruvate Hydratase