title: Abnormal maturation and differentiation of neocortical neurons in epileptogenic cortical malformation: unique distribution of layer-specific marker cells of focal cortical dysplasia and hemimegalencephaly.
abstract: Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are major causes of intractable epilepsy in children. The probable pathogenesis of FCD and HMG is the abnormal migration and differentiation of neurons. The aim of the present study was to clarify the abnormal cytoarchitecture, based on neuronal immaturation. Tissue samples were obtained from 16 FCD and seven HME patients, aged between 2 months and 12 years, who had been diagnosed as typical FCD and HME, following surgical treatment for intractable epilepsy. Paraffin-embedded sections were stained with the antibodies of three layer-markers that are usually present only during the fetal period, namely SATB2 (expressed in the upper layer of the normal fetal neocortex), FOXP1 (expressed in the 5th layer), and TBR1 (expressed in the 6th layer). In FCD, SATB2-positive (+) cells located in the middle and deep regions of FCD Ia and Ib, but only in the superficial region of FCD IIa and IIb. FOXP1+ cells diffusely located in the neocortex, especially the upper layer of FCD IIa and IIb. TBR1+ cells mainly located in the middle and deep regions, and also white matter. In FCD IIb, TBR1+ cells were in the superficial region. In HME, SATB2+ and FOXP1+ cells were found diffusely. TBR1+ cells were in the middle and deep regions. On the basis of continued expression of fetal cortical layer-specific markers in FCD and HME brains, the abnormal neocortical formation in both is likely to be the result of disrupted neuronal migration and dysmaturation. The expression pattern is different between FCD and HME.
authors: Epilepsy Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors: Asako
authors: A
authors: Arai
authors: Takashi
authors: T
authors: Saito
authors: Sae
authors: S
authors: Hanai
authors: Sayuri
authors: S
authors: Sukigara
authors: Shin
authors: S
authors: Nabatame
authors: Taisuke
authors: T
authors: Otsuki
authors: Eiji
authors: E
authors: Nakagawa
authors: Akio
authors: A
authors: Takahashi
authors: Yuu
authors: Y
authors: Kaneko
authors: Takanobu
authors: T
authors: Kaido
authors: Yuko
authors: Y
authors: Saito
authors: Kenji
authors: K
authors: Sugai
authors: Masayuki
authors: M
authors: Sasaki
authors: Yu-Ichi
authors: Y
authors: Goto
authors: Masayuki
authors: M
authors: Itoh
mesh_terms: D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007223:Infant; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism; D019579:Neocortex / Q000002:abnormalities / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D012097:Repressor Proteins / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D055815:Young Adult
chemical_list: C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D036961:Matrix Attachment Region Binding Proteins; D012097:Repressor Proteins; C521297:SATB2 protein, human; D020825:T-Box Domain Proteins; C574705:TBR1 protein, human; D014157:Transcription Factors