Arx revisited: involved in the development of GABAergic interneurons

The aristaless-related homeobox (Arx) transcription factor, located on the X chromosome, has been implicated in a wide range of neurological disorders, including intellectual disability and epilepsy, as well as diabetes and pancreatic developmental disorders. In the mouse brain, Arx is expressed not...

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Main Authors: Akio Tsuboi, Seiich Yoshihara
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1563515/full
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author Akio Tsuboi
Seiich Yoshihara
author_facet Akio Tsuboi
Seiich Yoshihara
author_sort Akio Tsuboi
collection DOAJ
description The aristaless-related homeobox (Arx) transcription factor, located on the X chromosome, has been implicated in a wide range of neurological disorders, including intellectual disability and epilepsy, as well as diabetes and pancreatic developmental disorders. In the mouse brain, Arx is expressed not only in the olfactory bulb (OB) and cerebral cortex progenitor cells but also in these gamma-aminobutyric acid (GABA)-releasing interneurons. In the initial study, constitutive Arx knockout (KO) mice showed aberrant migration and a reduction in GABAergic interneurons in the neonatal OB. However, constitutive Arx KO mice with perinatal lethality preclude further analysis in adolescent or adult mice. To overcome this, Arx-floxed mice have been crossed with Cre driver mice to generate conditional KO mice with selective Arx deletion in distinct interneuron progenitors. These studies have identified Arx as a key transcriptional regulator involved in the generation, fate determination, and migration of cortical interneurons. This review focuses on the critical role of Arx in the development of progenitor cells and the migration of interneurons in the mouse OB and cerebral cortex, and discusses differences in Arx mutant-based abnormality between mouse mutants and human patients.
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spelling doaj-art-fab8e7006bbc41efa4b4d55c7e6c737e2025-08-20T03:44:28ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-03-011310.3389/fcell.2025.15635151563515Arx revisited: involved in the development of GABAergic interneuronsAkio Tsuboi0Seiich Yoshihara1Department of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanLaboratory for Molecular Biology of Neural Systems, Medical Research Center, Nara Medical University, Kashihara, JapanThe aristaless-related homeobox (Arx) transcription factor, located on the X chromosome, has been implicated in a wide range of neurological disorders, including intellectual disability and epilepsy, as well as diabetes and pancreatic developmental disorders. In the mouse brain, Arx is expressed not only in the olfactory bulb (OB) and cerebral cortex progenitor cells but also in these gamma-aminobutyric acid (GABA)-releasing interneurons. In the initial study, constitutive Arx knockout (KO) mice showed aberrant migration and a reduction in GABAergic interneurons in the neonatal OB. However, constitutive Arx KO mice with perinatal lethality preclude further analysis in adolescent or adult mice. To overcome this, Arx-floxed mice have been crossed with Cre driver mice to generate conditional KO mice with selective Arx deletion in distinct interneuron progenitors. These studies have identified Arx as a key transcriptional regulator involved in the generation, fate determination, and migration of cortical interneurons. This review focuses on the critical role of Arx in the development of progenitor cells and the migration of interneurons in the mouse OB and cerebral cortex, and discusses differences in Arx mutant-based abnormality between mouse mutants and human patients.https://www.frontiersin.org/articles/10.3389/fcell.2025.1563515/fullArxtranscription factorolfactory bulbcerebral cortexinterneuron
spellingShingle Akio Tsuboi
Seiich Yoshihara
Arx revisited: involved in the development of GABAergic interneurons
Frontiers in Cell and Developmental Biology
Arx
transcription factor
olfactory bulb
cerebral cortex
interneuron
title Arx revisited: involved in the development of GABAergic interneurons
title_full Arx revisited: involved in the development of GABAergic interneurons
title_fullStr Arx revisited: involved in the development of GABAergic interneurons
title_full_unstemmed Arx revisited: involved in the development of GABAergic interneurons
title_short Arx revisited: involved in the development of GABAergic interneurons
title_sort arx revisited involved in the development of gabaergic interneurons
topic Arx
transcription factor
olfactory bulb
cerebral cortex
interneuron
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1563515/full
work_keys_str_mv AT akiotsuboi arxrevisitedinvolvedinthedevelopmentofgabaergicinterneurons
AT seiichyoshihara arxrevisitedinvolvedinthedevelopmentofgabaergicinterneurons