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Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex

Genetic evidence indicates that haploinsufficiency of ARID1B causes intellectual disability (ID) and autism spectrum disorder (ASD), but the neural function of ARID1B is largely unknown. Using both conditional and global Arid1b knockout mouse strains, we examined the role of ARID1B in neural progeni...

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Autores principales: Moffat, Jeffrey J., Jung, Eui-Man, Ka, Minhan, Jeon, Byeong Tak, Lee, Hyunkyoung, Kim, Woo-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886865/
https://www.ncbi.nlm.nih.gov/pubmed/33594090
http://dx.doi.org/10.1038/s41598-021-82974-y
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author Moffat, Jeffrey J.
Jung, Eui-Man
Ka, Minhan
Jeon, Byeong Tak
Lee, Hyunkyoung
Kim, Woo-Yang
author_facet Moffat, Jeffrey J.
Jung, Eui-Man
Ka, Minhan
Jeon, Byeong Tak
Lee, Hyunkyoung
Kim, Woo-Yang
author_sort Moffat, Jeffrey J.
collection PubMed
description Genetic evidence indicates that haploinsufficiency of ARID1B causes intellectual disability (ID) and autism spectrum disorder (ASD), but the neural function of ARID1B is largely unknown. Using both conditional and global Arid1b knockout mouse strains, we examined the role of ARID1B in neural progenitors. We detected an overall decrease in the proliferation of cortical and ventral neural progenitors following homozygous deletion of Arid1b, as well as altered cell cycle regulation and increased cell death. Each of these phenotypes was more pronounced in ventral neural progenitors. Furthermore, we observed decreased nuclear localization of β-catenin in Arid1b-deficient neurons. Conditional homozygous deletion of Arid1b in ventral neural progenitors led to pronounced ID- and ASD-like behaviors in mice, whereas the deletion in cortical neural progenitors resulted in minor cognitive deficits. This study suggests an essential role for ARID1B in forebrain neurogenesis and clarifies its more pronounced role in inhibitory neural progenitors. Our findings also provide insights into the pathogenesis of ID and ASD.
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spelling pubmed-78868652021-02-18 Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex Moffat, Jeffrey J. Jung, Eui-Man Ka, Minhan Jeon, Byeong Tak Lee, Hyunkyoung Kim, Woo-Yang Sci Rep Article Genetic evidence indicates that haploinsufficiency of ARID1B causes intellectual disability (ID) and autism spectrum disorder (ASD), but the neural function of ARID1B is largely unknown. Using both conditional and global Arid1b knockout mouse strains, we examined the role of ARID1B in neural progenitors. We detected an overall decrease in the proliferation of cortical and ventral neural progenitors following homozygous deletion of Arid1b, as well as altered cell cycle regulation and increased cell death. Each of these phenotypes was more pronounced in ventral neural progenitors. Furthermore, we observed decreased nuclear localization of β-catenin in Arid1b-deficient neurons. Conditional homozygous deletion of Arid1b in ventral neural progenitors led to pronounced ID- and ASD-like behaviors in mice, whereas the deletion in cortical neural progenitors resulted in minor cognitive deficits. This study suggests an essential role for ARID1B in forebrain neurogenesis and clarifies its more pronounced role in inhibitory neural progenitors. Our findings also provide insights into the pathogenesis of ID and ASD. Nature Publishing Group UK 2021-02-16 /pmc/articles/PMC7886865/ /pubmed/33594090 http://dx.doi.org/10.1038/s41598-021-82974-y Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Moffat, Jeffrey J.
Jung, Eui-Man
Ka, Minhan
Jeon, Byeong Tak
Lee, Hyunkyoung
Kim, Woo-Yang
Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex
title Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex
title_full Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex
title_fullStr Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex
title_full_unstemmed Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex
title_short Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex
title_sort differential roles of arid1b in excitatory and inhibitory neural progenitors in the developing cortex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886865/
https://www.ncbi.nlm.nih.gov/pubmed/33594090
http://dx.doi.org/10.1038/s41598-021-82974-y
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