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Regulation of Neurogenesis in Mouse Brain by HMGB1
The High Mobility Group Box 1 (HMGB1) is the most abundant nuclear nonhistone protein that is involved in transcription regulation. In addition, HMGB1 has previously been found as an extracellularly acting protein enhancing neurite outgrowth in cultured neurons. Although HMGB1 is widely expressed in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407245/ https://www.ncbi.nlm.nih.gov/pubmed/32708917 http://dx.doi.org/10.3390/cells9071714 |
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author | Zhao, Xiang Rouhiainen, Ari Li, Zhilin Guo, Su Rauvala, Heikki |
author_facet | Zhao, Xiang Rouhiainen, Ari Li, Zhilin Guo, Su Rauvala, Heikki |
author_sort | Zhao, Xiang |
collection | PubMed |
description | The High Mobility Group Box 1 (HMGB1) is the most abundant nuclear nonhistone protein that is involved in transcription regulation. In addition, HMGB1 has previously been found as an extracellularly acting protein enhancing neurite outgrowth in cultured neurons. Although HMGB1 is widely expressed in the developing central nervous system of vertebrates and invertebrates, its function in the developing mouse brain is poorly understood. Here, we have analyzed developmental defects of the HMGB1 null mouse forebrain, and further examined our findings in ex vivo brain cell cultures. We find that HMGB1 is required for the proliferation and differentiation of neuronal stem cells/progenitor cells. Enhanced apoptosis is also found in the neuronal cells lacking HMGB1. Moreover, HMGB1 depletion disrupts Wnt/β-catenin signaling and the expression of transcription factors in the developing cortex, including Foxg1, Tbr2, Emx2, and Lhx6. Finally, HMGB1 null mice display aberrant expression of CXCL12/CXCR4 and reduced RAGE signaling. In conclusion, HMGB1 plays a critical role in mammalian neurogenesis and brain development. |
format | Online Article Text |
id | pubmed-7407245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74072452020-08-11 Regulation of Neurogenesis in Mouse Brain by HMGB1 Zhao, Xiang Rouhiainen, Ari Li, Zhilin Guo, Su Rauvala, Heikki Cells Article The High Mobility Group Box 1 (HMGB1) is the most abundant nuclear nonhistone protein that is involved in transcription regulation. In addition, HMGB1 has previously been found as an extracellularly acting protein enhancing neurite outgrowth in cultured neurons. Although HMGB1 is widely expressed in the developing central nervous system of vertebrates and invertebrates, its function in the developing mouse brain is poorly understood. Here, we have analyzed developmental defects of the HMGB1 null mouse forebrain, and further examined our findings in ex vivo brain cell cultures. We find that HMGB1 is required for the proliferation and differentiation of neuronal stem cells/progenitor cells. Enhanced apoptosis is also found in the neuronal cells lacking HMGB1. Moreover, HMGB1 depletion disrupts Wnt/β-catenin signaling and the expression of transcription factors in the developing cortex, including Foxg1, Tbr2, Emx2, and Lhx6. Finally, HMGB1 null mice display aberrant expression of CXCL12/CXCR4 and reduced RAGE signaling. In conclusion, HMGB1 plays a critical role in mammalian neurogenesis and brain development. MDPI 2020-07-17 /pmc/articles/PMC7407245/ /pubmed/32708917 http://dx.doi.org/10.3390/cells9071714 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhao, Xiang Rouhiainen, Ari Li, Zhilin Guo, Su Rauvala, Heikki Regulation of Neurogenesis in Mouse Brain by HMGB1 |
title | Regulation of Neurogenesis in Mouse Brain by HMGB1 |
title_full | Regulation of Neurogenesis in Mouse Brain by HMGB1 |
title_fullStr | Regulation of Neurogenesis in Mouse Brain by HMGB1 |
title_full_unstemmed | Regulation of Neurogenesis in Mouse Brain by HMGB1 |
title_short | Regulation of Neurogenesis in Mouse Brain by HMGB1 |
title_sort | regulation of neurogenesis in mouse brain by hmgb1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407245/ https://www.ncbi.nlm.nih.gov/pubmed/32708917 http://dx.doi.org/10.3390/cells9071714 |
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