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.
authors.affiliation: Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Colasante
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sessa
authors.forename: Stefania
authors.initials: S
authors.lastname: Crispi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Calogero
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mansouri
authors.forename: Patrick
authors.initials: P
authors.lastname: Collombat
authors.forename: Vania
authors.initials: V
authors.lastname: Broccoli
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D002465:Cell Movement; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009474:Neurons / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013687:Telencephalon / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C469265:ARX protein, mouse; C110117:Ebf3 protein, mouse; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors