Doublecortin-like (DCL) expression in focal cortical dysplasia and cortical tubers.
OBJECTIVE
Focal cortical dysplasia type IIB (FCD IIB) and cortical tubers of patients with tuberous sclerosis complex (TSC) are malformations of cortical development that are frequently associated with intractable epilepsy. Their histopathologic and molecular features suggest developmental abnormalities during the early stages of cortical development, which may involve neural progenitor cells. The aim of our study was to define the expression and cell-specific distribution of doublecortin-like (DCL), a protein critically involved in neuronal division and radial migration during early corticogenesis, in both FCD and TSC.


METHODS
DCL was studied in epilepsy surgery cases with FCD IIB (n = 8) and TSC (cortical tubers; n = 8) using immunocytochemistry, confocal analysis, and Western blotting.


RESULTS
Autopsy and surgical control neocortical specimens were characterized by modest DCL immunoreactivity (IR) throughout all cortical layers, but DCL IR was not detectable in the white matter. Balloon cells (BCs) in FCD and giant cells (GCs) in TSC expressed strong DCL IR. Most of the large dysplastic neurons (DNs) were positive for DCL in both FCD and TSC. Coexpression of DCL with the neural progenitor or neuroblast markers nestin, GFAPdelta, and doublecortin was observed in both FCD and TSC specimens. The increased DCL expression within the dysplastic cortex, compared to control cortex, was confirmed by Western blot analysis.


CONCLUSIONS
The prominent postnatal expression of DCL by BCs/GCs and DNs in FCD and TSC supports an important role for this microtubule associated protein, also during early human cortical development, which could be relevant to the pathogenesis of these developmental glioneuronal malformations.
Boer
Karin
K
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Lucassen
Paul J
PJ
Spliet
Wim G M
WG
Vreugdenhil
Erno
E
van Rijen
Peter C
PC
Troost
Dirk
D
Jansen
Floor E
FE
Aronica
Eleonora
E
D000293:Adolescent; D000328:Adult; D001344:Autopsy; D002540:Cerebral Cortex / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D000089622:Doublecortin Domain Proteins; D004827:Epilepsy / Q000235:genetics* / Q000276:immunology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D015726:Giant Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D054220:Malformations of Cortical Development / Q000235:genetics* / Q000276:immunology; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D055495:Neurogenesis / Q000235:genetics / Q000276:immunology; D009474:Neurons / Q000276:immunology / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics* / Q000276:immunology; D013234:Stem Cells / Q000276:immunology / Q000502:physiology; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000276:immunology
D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides