INTERNEXIN, MAP1B, AND NESTIN IN CORTICAL DYSPLASIA AS MARKERS OF DEVELOPMENTAL MATURITY

Cortical dysplasias (CD) are characterized histologically by disorgani zed cortical lamination and abnormally shaped neurons. We hypothesized that neurons within CD have failed to differentiate fully and may exp ress proteins such as cytoskeletal elements characteristic of immature cells. Disrupted expression of certain cytoskeletal proteins, which h ave been implicated in neuronal polarity, process outgrowth, and migra tion, could result in disorganized cortical lamination. Thus, we probe d two CD subtypes, focal CD (FCD) and hemimegalencephaly (HME), with a ntibodies 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-associat ed protein 1B (MAP1B) and the intermediate filament (IF) protein nesti n are enriched in neural progenitors, whereas MAP2B, phosphorylated an d non-phosphorylated forms of medium (NFM) and high (NFH) molecular we ight 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 abund ant in the most abnormally shaped neurons that populated dysplastic re gions than in adjacent regions exhibiting milder cytoarchitectural abn ormalities or control cortex. Nestin immunoreactivity was noted in lar ge dysplastic and heterotopic neurons within the deeper cortical layer s of CD specimens but not in normal cortex. In contrast, neurons in CD specimens also expressed cytoskeletal markers characteristic of diffe rentiated neurons such as NF subunits and MAP2B. These findings sugges t that the cytoarchitectural abnormalities in CD may reflect pathophys iological changes in the developing brain that disrupt expression of s everal key components of the neuronal cytoskeleton and may contribute to impaired migration of cortical neurons.