Abstract
To define distinctive features of nodular heterotopia in specimens derived from drug-resistant patients with epilepsy by evaluating mRNA expression of three different layer-specific markers: Rorbeta, Er81, and Nurr1. We analyzed the expression profile of these genes, recognized as markers mainly expressed in layer IV for Rorbeta, in layer V for Er81, and in layer VI for Nurr1, in surgical samples from 14 epileptic patients, using in situ hybridization. Six patients had subcortical nodular heterotopia and 8 patients were controls. The intrinsic organization of nodular formations and of the overlaying neocortex was assessed. In all patients, the 3 selected genes showed high cortical laminar specificity. In subcortical nodular heterotopia, the different gene expression profiles revealed a rudimentary laminar organization of the nodules. In the overlaying cortex, fewer cells expressed the 3 genes in the appropriate specific layer as compared to controls. These data provide new insights into possible ontogenetic mechanisms of nodular heterotopia formation and show the potential role of layer-specific markers to elucidate the neuropathology of malformations of cortical development.
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