Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity

Gaia Colasante, Alessandro Sessa, Stefania Crispi, Raffaele Calogero, Ahmed Mansouri, Patrick Collombat, Vania Broccoli

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The homeobox-containing gene Arx is expressed during ventral telencephalon development and required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose symptoms are compatible with the loss of cortical interneurons and altered basal ganglia-related activities. Herein, we report the identification of a number of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Our analyses revealed a striking ectopic expression in the ganglionic eminences of several of these genes normally at most marginally expressed in the ventral telencephalon. Among them, Ebf3 was functionally analyzed. Thus, its ectopic expression in ventral telencephalon was found to prevent neuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissues partially rescues tangential cell movement. Together, these data provide new insights into the molecular pathways regulated by Arx during telencephalon development.

Original languageEnglish
Pages (from-to)59-71
Number of pages13
JournalDevelopmental Biology
Volume334
Issue number1
DOIs
Publication statusPublished - Oct 1 2009

Fingerprint

Telencephalon
Interneurons
Genes
Homeobox Genes
Olfactory Bulb
Neurologic Manifestations
Basal Ganglia
Cerebral Cortex
Cell Movement
Gene Expression
Ectopic Gene Expression

Keywords

  • Arx
  • Basal ganglia
  • Cell migration
  • Expression profile
  • Forebrain
  • GABA
  • Gene expression
  • Lissencephaly
  • Neurogenesis
  • Telencephalon
  • Transcription factor
  • West syndrome

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Cite this

Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity. / Colasante, Gaia; Sessa, Alessandro; Crispi, Stefania; Calogero, Raffaele; Mansouri, Ahmed; Collombat, Patrick; Broccoli, Vania.

In: Developmental Biology, Vol. 334, No. 1, 01.10.2009, p. 59-71.

Research output: Contribution to journalArticle

Colasante, Gaia ; Sessa, Alessandro ; Crispi, Stefania ; Calogero, Raffaele ; Mansouri, Ahmed ; Collombat, Patrick ; Broccoli, Vania. / Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity. In: Developmental Biology. 2009 ; Vol. 334, No. 1. pp. 59-71.
@article{62dcb8cc480e477eb8fb7d056bd96295,
title = "Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity",
abstract = "The homeobox-containing gene Arx is expressed during ventral telencephalon development and required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose symptoms are compatible with the loss of cortical interneurons and altered basal ganglia-related activities. Herein, we report the identification of a number of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Our analyses revealed a striking ectopic expression in the ganglionic eminences of several of these genes normally at most marginally expressed in the ventral telencephalon. Among them, Ebf3 was functionally analyzed. Thus, its ectopic expression in ventral telencephalon was found to prevent neuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissues partially rescues tangential cell movement. Together, these data provide new insights into the molecular pathways regulated by Arx during telencephalon development.",
keywords = "Arx, Basal ganglia, Cell migration, Expression profile, Forebrain, GABA, Gene expression, Lissencephaly, Neurogenesis, Telencephalon, Transcription factor, West syndrome",
author = "Gaia Colasante and Alessandro Sessa and Stefania Crispi and Raffaele Calogero and Ahmed Mansouri and Patrick Collombat and Vania Broccoli",
year = "2009",
month = "10",
day = "1",
doi = "10.1016/j.ydbio.2009.07.014",
language = "English",
volume = "334",
pages = "59--71",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity

AU - Colasante, Gaia

AU - Sessa, Alessandro

AU - Crispi, Stefania

AU - Calogero, Raffaele

AU - Mansouri, Ahmed

AU - Collombat, Patrick

AU - Broccoli, Vania

PY - 2009/10/1

Y1 - 2009/10/1

N2 - The homeobox-containing gene Arx is expressed during ventral telencephalon development and required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose symptoms are compatible with the loss of cortical interneurons and altered basal ganglia-related activities. Herein, we report the identification of a number of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Our analyses revealed a striking ectopic expression in the ganglionic eminences of several of these genes normally at most marginally expressed in the ventral telencephalon. Among them, Ebf3 was functionally analyzed. Thus, its ectopic expression in ventral telencephalon was found to prevent neuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissues partially rescues tangential cell movement. Together, these data provide new insights into the molecular pathways regulated by Arx during telencephalon development.

AB - The homeobox-containing gene Arx is expressed during ventral telencephalon development and required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose symptoms are compatible with the loss of cortical interneurons and altered basal ganglia-related activities. Herein, we report the identification of a number of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Our analyses revealed a striking ectopic expression in the ganglionic eminences of several of these genes normally at most marginally expressed in the ventral telencephalon. Among them, Ebf3 was functionally analyzed. Thus, its ectopic expression in ventral telencephalon was found to prevent neuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissues partially rescues tangential cell movement. Together, these data provide new insights into the molecular pathways regulated by Arx during telencephalon development.

KW - Arx

KW - Basal ganglia

KW - Cell migration

KW - Expression profile

KW - Forebrain

KW - GABA

KW - Gene expression

KW - Lissencephaly

KW - Neurogenesis

KW - Telencephalon

KW - Transcription factor

KW - West syndrome

UR - http://www.scopus.com/inward/record.url?scp=69949134504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69949134504&partnerID=8YFLogxK

U2 - 10.1016/j.ydbio.2009.07.014

DO - 10.1016/j.ydbio.2009.07.014

M3 - Article

C2 - 19627984

AN - SCOPUS:69949134504

VL - 334

SP - 59

EP - 71

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 1

ER -