Internexin, MAP1B, and nestin in cortical dysplasia as markers of developmental maturity

Cortical dysplasias (CD) are characterized histologically by disorganized cortical lamination and abnormally shaped neurons. We hypothesized that neurons within CD have failed to differentiate fully and may express proteins such as cytoskeletal elements characteristic of immature cells. Disrupted expression of certain cytoskeletal proteins, which have been implicated in neuronal polarity, process outgrowth, and migration, could result in disorganized cortical lamination. Thus, we probed two CD subtypes, focal CD (FCD) and hemimegalencephaly (HME), with antibodies specific for cytoskeletal proteins that are developmentally regulated in neural progenitor cells and neurons to define more fully the developmental phenotype of neurons within CD. Microtubule-associated protein 1B (MAP1B) and the intermediate filament (IF) protein nestin are enriched in neural progenitors, whereas MAP2B, phosphorylated and non-phosphorylated forms of medium (NFM) and high (NFH) molecular weight neurofilament (NF) proteins, as well as the light NF subunit (NFL) and the IF protein alpha internexin are expressed in developing and mature neurons. Immunolabeling for internexin and MAP1B was more abundant in the most abnormally shaped neurons that populated dysplastic regions than in adjacent regions exhibiting milder cytoarchitectural abnormalities or control cortex. Nestin immunoreactivity was noted in large dysplastic and heterotopic neurons within the deeper cortical layers of CD specimens but not in normal cortex. In contrast, neurons in CD specimens also expressed cytoskeletal markers characteristic of differentiated neurons such as NF subunits and MAP2B. These findings suggest that the cytoarchitectural abnormalities in CD may reflect pathophysiological changes in the developing brain that disrupt expression of several key components of the neuronal cytoskeleton and may contribute to impaired migration of cortical neurons.