title: Layer-specific genes reveal a rudimentary laminar pattern in human nodular heterotopia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, 20133 Milan, Italy. garbelli.r@istituto-besta.it
authors.forename: R
authors.initials: R
authors.lastname: Garbelli
authors.forename: L
authors.initials: L
authors.lastname: Rossini
authors.forename: R F
authors.initials: RF
authors.lastname: Moroni
authors.forename: A
authors.initials: A
authors.lastname: Watakabe
authors.forename: T
authors.initials: T
authors.lastname: Yamamori
authors.forename: L
authors.initials: L
authors.lastname: Tassi
authors.forename: M
authors.initials: M
authors.lastname: Bramerio
authors.forename: G L
authors.initials: GL
authors.lastname: Russo
authors.forename: C
authors.initials: C
authors.lastname: Frassoni
authors.forename: R
authors.initials: R
authors.lastname: Spreafico
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000473:pathology* / Q000502:physiology; D002648:Child; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D054220:Malformations of Cortical Development / Q000235:genetics / Q000473:pathology; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D054091:Periventricular Nodular Heterotopia / Q000235:genetics* / Q000473:pathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; D005819:Genetic Markers; C539882:NR4A2 protein, human; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; C539740:RORB protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors