Layer-specific gene expression in epileptogenic type II focal cortical dysplasia: normal-looking neurons reveal the presence of a hidden laminar organization

Laura Rossini, Valentina Medici, Laura Tassi, Francesco Cardinale, Giovanni Tringali, Manuela Bramerio, Flavio Villani, Roberto Spreafico, Rita Garbelli

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

BACKGROUND: Type II focal cortical dysplasias (FCDs) are malformations of cortical development characterised by the disorganisation of the normal neocortical structure and the presence of dysmorphic neurons (DNs) and balloon cells (BCs). The pathogenesis of FCDs has not yet been clearly established, although a number of histopathological patterns and molecular findings suggest that they may be due to abnormal neuronal and glial proliferation and migration processes.In order to gain further insights into cortical layering disruption and investigate the origin of DNs and BCs, we used in situ RNA hybridisation of human surgical specimens with a neuropathologically definite diagnosis of Type IIa/b FCD and a panel of layer-specific genes (LSGs) whose expression covers all cortical layers. We also used anti-phospho-S6 ribosomal protein antibody to investigate mTOR pathway hyperactivation.

RESULTS: LSGs were expressed in both normal and abnormal cells (BCs and DNs) but their distribution was different. Normal-looking neurons, which were visibly reduced in the core of the lesion, were apparently located in the appropriate cortical laminae thus indicating a partial laminar organisation. On the contrary, DNs and BCs, labelled with anti-phospho-S6 ribosomal protein antibody, were spread throughout the cortex without any apparent rule and showed a highly variable LSG expression pattern. Moreover, LSGs did not reveal any differences between Type IIa and IIb FCD.

CONCLUSION: These findings suggest the existence of hidden cortical lamination involving normal-looking neurons, which retain their ability to migrate correctly in the cortex, unlike DNs which, in addition to their morphological abnormalities and mTOR hyperactivation, show an altered migratory pattern.Taken together these data suggest that an external or environmental hit affecting selected precursor cells during the very early stages of cortical development may disrupt normal cortical development.

Original languageEnglish
Pages (from-to)45
Number of pages1
JournalActa neuropathologica communications
Volume2
DOIs
Publication statusPublished - 2014

Fingerprint

Malformations of Cortical Development
Gene Expression
Neurons
Ribosomal Protein S6
Antibodies
Focal cortical dysplasia of Taylor
Neuroglia
Genes
In Situ Hybridization
RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Layer-specific gene expression in epileptogenic type II focal cortical dysplasia : normal-looking neurons reveal the presence of a hidden laminar organization. / Rossini, Laura; Medici, Valentina; Tassi, Laura; Cardinale, Francesco; Tringali, Giovanni; Bramerio, Manuela; Villani, Flavio; Spreafico, Roberto; Garbelli, Rita.

In: Acta neuropathologica communications, Vol. 2, 2014, p. 45.

Research output: Contribution to journalArticle

@article{f311f7361d7b45099a192696308a86cf,
title = "Layer-specific gene expression in epileptogenic type II focal cortical dysplasia: normal-looking neurons reveal the presence of a hidden laminar organization",
abstract = "BACKGROUND: Type II focal cortical dysplasias (FCDs) are malformations of cortical development characterised by the disorganisation of the normal neocortical structure and the presence of dysmorphic neurons (DNs) and balloon cells (BCs). The pathogenesis of FCDs has not yet been clearly established, although a number of histopathological patterns and molecular findings suggest that they may be due to abnormal neuronal and glial proliferation and migration processes.In order to gain further insights into cortical layering disruption and investigate the origin of DNs and BCs, we used in situ RNA hybridisation of human surgical specimens with a neuropathologically definite diagnosis of Type IIa/b FCD and a panel of layer-specific genes (LSGs) whose expression covers all cortical layers. We also used anti-phospho-S6 ribosomal protein antibody to investigate mTOR pathway hyperactivation.RESULTS: LSGs were expressed in both normal and abnormal cells (BCs and DNs) but their distribution was different. Normal-looking neurons, which were visibly reduced in the core of the lesion, were apparently located in the appropriate cortical laminae thus indicating a partial laminar organisation. On the contrary, DNs and BCs, labelled with anti-phospho-S6 ribosomal protein antibody, were spread throughout the cortex without any apparent rule and showed a highly variable LSG expression pattern. Moreover, LSGs did not reveal any differences between Type IIa and IIb FCD.CONCLUSION: These findings suggest the existence of hidden cortical lamination involving normal-looking neurons, which retain their ability to migrate correctly in the cortex, unlike DNs which, in addition to their morphological abnormalities and mTOR hyperactivation, show an altered migratory pattern.Taken together these data suggest that an external or environmental hit affecting selected precursor cells during the very early stages of cortical development may disrupt normal cortical development.",
author = "Laura Rossini and Valentina Medici and Laura Tassi and Francesco Cardinale and Giovanni Tringali and Manuela Bramerio and Flavio Villani and Roberto Spreafico and Rita Garbelli",
year = "2014",
doi = "10.1186/2051-5960-2-45",
language = "English",
volume = "2",
pages = "45",
journal = "Acta neuropathologica communications",
issn = "2051-5960",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Layer-specific gene expression in epileptogenic type II focal cortical dysplasia

T2 - normal-looking neurons reveal the presence of a hidden laminar organization

AU - Rossini, Laura

AU - Medici, Valentina

AU - Tassi, Laura

AU - Cardinale, Francesco

AU - Tringali, Giovanni

AU - Bramerio, Manuela

AU - Villani, Flavio

AU - Spreafico, Roberto

AU - Garbelli, Rita

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Type II focal cortical dysplasias (FCDs) are malformations of cortical development characterised by the disorganisation of the normal neocortical structure and the presence of dysmorphic neurons (DNs) and balloon cells (BCs). The pathogenesis of FCDs has not yet been clearly established, although a number of histopathological patterns and molecular findings suggest that they may be due to abnormal neuronal and glial proliferation and migration processes.In order to gain further insights into cortical layering disruption and investigate the origin of DNs and BCs, we used in situ RNA hybridisation of human surgical specimens with a neuropathologically definite diagnosis of Type IIa/b FCD and a panel of layer-specific genes (LSGs) whose expression covers all cortical layers. We also used anti-phospho-S6 ribosomal protein antibody to investigate mTOR pathway hyperactivation.RESULTS: LSGs were expressed in both normal and abnormal cells (BCs and DNs) but their distribution was different. Normal-looking neurons, which were visibly reduced in the core of the lesion, were apparently located in the appropriate cortical laminae thus indicating a partial laminar organisation. On the contrary, DNs and BCs, labelled with anti-phospho-S6 ribosomal protein antibody, were spread throughout the cortex without any apparent rule and showed a highly variable LSG expression pattern. Moreover, LSGs did not reveal any differences between Type IIa and IIb FCD.CONCLUSION: These findings suggest the existence of hidden cortical lamination involving normal-looking neurons, which retain their ability to migrate correctly in the cortex, unlike DNs which, in addition to their morphological abnormalities and mTOR hyperactivation, show an altered migratory pattern.Taken together these data suggest that an external or environmental hit affecting selected precursor cells during the very early stages of cortical development may disrupt normal cortical development.

AB - BACKGROUND: Type II focal cortical dysplasias (FCDs) are malformations of cortical development characterised by the disorganisation of the normal neocortical structure and the presence of dysmorphic neurons (DNs) and balloon cells (BCs). The pathogenesis of FCDs has not yet been clearly established, although a number of histopathological patterns and molecular findings suggest that they may be due to abnormal neuronal and glial proliferation and migration processes.In order to gain further insights into cortical layering disruption and investigate the origin of DNs and BCs, we used in situ RNA hybridisation of human surgical specimens with a neuropathologically definite diagnosis of Type IIa/b FCD and a panel of layer-specific genes (LSGs) whose expression covers all cortical layers. We also used anti-phospho-S6 ribosomal protein antibody to investigate mTOR pathway hyperactivation.RESULTS: LSGs were expressed in both normal and abnormal cells (BCs and DNs) but their distribution was different. Normal-looking neurons, which were visibly reduced in the core of the lesion, were apparently located in the appropriate cortical laminae thus indicating a partial laminar organisation. On the contrary, DNs and BCs, labelled with anti-phospho-S6 ribosomal protein antibody, were spread throughout the cortex without any apparent rule and showed a highly variable LSG expression pattern. Moreover, LSGs did not reveal any differences between Type IIa and IIb FCD.CONCLUSION: These findings suggest the existence of hidden cortical lamination involving normal-looking neurons, which retain their ability to migrate correctly in the cortex, unlike DNs which, in addition to their morphological abnormalities and mTOR hyperactivation, show an altered migratory pattern.Taken together these data suggest that an external or environmental hit affecting selected precursor cells during the very early stages of cortical development may disrupt normal cortical development.

UR - http://www.scopus.com/inward/record.url?scp=84921435661&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921435661&partnerID=8YFLogxK

U2 - 10.1186/2051-5960-2-45

DO - 10.1186/2051-5960-2-45

M3 - Article

C2 - 24735483

AN - SCOPUS:84921435661

VL - 2

SP - 45

JO - Acta neuropathologica communications

JF - Acta neuropathologica communications

SN - 2051-5960

ER -