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Arx Expression Suppresses Ventralization of the Developing Dorsal Forebrain
Early brain development requires a tight orchestration between neural tube patterning and growth. How pattern formation and brain growth are coordinated is incompletely understood. Previously we showed that aristaless-related homeobox (ARX), a paired-like transcription factor, regulates cortical pro...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338776/ https://www.ncbi.nlm.nih.gov/pubmed/30659230 http://dx.doi.org/10.1038/s41598-018-36194-6 |
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author | Lim, Youngshin Cho, Il-Taeg Shi, Xiuyu Grinspan, Judith B. Cho, Ginam Golden, Jeffrey A. |
author_facet | Lim, Youngshin Cho, Il-Taeg Shi, Xiuyu Grinspan, Judith B. Cho, Ginam Golden, Jeffrey A. |
author_sort | Lim, Youngshin |
collection | PubMed |
description | Early brain development requires a tight orchestration between neural tube patterning and growth. How pattern formation and brain growth are coordinated is incompletely understood. Previously we showed that aristaless-related homeobox (ARX), a paired-like transcription factor, regulates cortical progenitor pool expansion by repressing an inhibitor of cell cycle progression. Here we show that ARX participates in establishing dorsoventral identity in the mouse forebrain. In Arx mutant mice, ventral genes, including Olig2, are ectopically expressed dorsally. Furthermore, Gli1 is upregulated, suggesting an ectopic activation of SHH signaling. We show that the ectopic Olig2 expression can be repressed by blocking SHH signaling, implicating a role for SHH signaling in Olig2 induction. We further demonstrate that the ectopic Olig2 accounts for the reduced Pax6 and Tbr2 expression, both dorsal specific genes essential for cortical progenitor cell proliferation. These data suggest a link between the control of dorsoventral identity of progenitor cells and the control of their proliferation. In summary, our data demonstrate that ARX functions in a gene regulatory network integrating normal forebrain patterning and growth, providing important insight into how mutations in ARX can disrupt multiple aspects of brain development and thus generate a wide spectrum of neurodevelopmental phenotypes observed in human patients. |
format | Online Article Text |
id | pubmed-6338776 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63387762019-01-23 Arx Expression Suppresses Ventralization of the Developing Dorsal Forebrain Lim, Youngshin Cho, Il-Taeg Shi, Xiuyu Grinspan, Judith B. Cho, Ginam Golden, Jeffrey A. Sci Rep Article Early brain development requires a tight orchestration between neural tube patterning and growth. How pattern formation and brain growth are coordinated is incompletely understood. Previously we showed that aristaless-related homeobox (ARX), a paired-like transcription factor, regulates cortical progenitor pool expansion by repressing an inhibitor of cell cycle progression. Here we show that ARX participates in establishing dorsoventral identity in the mouse forebrain. In Arx mutant mice, ventral genes, including Olig2, are ectopically expressed dorsally. Furthermore, Gli1 is upregulated, suggesting an ectopic activation of SHH signaling. We show that the ectopic Olig2 expression can be repressed by blocking SHH signaling, implicating a role for SHH signaling in Olig2 induction. We further demonstrate that the ectopic Olig2 accounts for the reduced Pax6 and Tbr2 expression, both dorsal specific genes essential for cortical progenitor cell proliferation. These data suggest a link between the control of dorsoventral identity of progenitor cells and the control of their proliferation. In summary, our data demonstrate that ARX functions in a gene regulatory network integrating normal forebrain patterning and growth, providing important insight into how mutations in ARX can disrupt multiple aspects of brain development and thus generate a wide spectrum of neurodevelopmental phenotypes observed in human patients. Nature Publishing Group UK 2019-01-18 /pmc/articles/PMC6338776/ /pubmed/30659230 http://dx.doi.org/10.1038/s41598-018-36194-6 Text en © The Author(s) 2019 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lim, Youngshin Cho, Il-Taeg Shi, Xiuyu Grinspan, Judith B. Cho, Ginam Golden, Jeffrey A. Arx Expression Suppresses Ventralization of the Developing Dorsal Forebrain |
title | Arx Expression Suppresses Ventralization of the Developing Dorsal Forebrain |
title_full | Arx Expression Suppresses Ventralization of the Developing Dorsal Forebrain |
title_fullStr | Arx Expression Suppresses Ventralization of the Developing Dorsal Forebrain |
title_full_unstemmed | Arx Expression Suppresses Ventralization of the Developing Dorsal Forebrain |
title_short | Arx Expression Suppresses Ventralization of the Developing Dorsal Forebrain |
title_sort | arx expression suppresses ventralization of the developing dorsal forebrain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338776/ https://www.ncbi.nlm.nih.gov/pubmed/30659230 http://dx.doi.org/10.1038/s41598-018-36194-6 |
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