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アイテム
Histone Deacetylases Control Neurogenesis in Embryonic Brain by Inhibition of BMP2/4 Signaling
http://hdl.handle.net/10228/5982
http://hdl.handle.net/10228/5982f15e66b2-db6a-4bf6-8c7d-16d64978c554
| 名前 / ファイル | ライセンス | アクション |
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pone7_e2668.pdf (1.1 MB)
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| アイテムタイプ | 学術雑誌論文 = Journal Article(1) | |||||
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| 公開日 | 2017-01-19 | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| タイトル | ||||||
| タイトル | Histone Deacetylases Control Neurogenesis in Embryonic Brain by Inhibition of BMP2/4 Signaling | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 著者 |
Shakèd, Maya
× Shakèd, Maya× Weissmüller, Kathrin× Svoboda, Hanno× Hortschansky, Peter× 西野, 憲和× Wölfl, Stefan× Tucker, Kerry L. |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | BackgroundHistone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs) lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain.Principal FindingsAs a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited.ConclusionsOur results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical neurogenesis. The results also suggest that HDACs may regulate the developmental switch from neurogenesis to astrogliogenesis that occurs in late gestation. | |||||
| 言語 | en | |||||
| 書誌情報 |
PLoS ONE 巻 3, 号 7, p. e2668-1-e2668-19, 発行日 2008-07-16 |
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| 出版社 | ||||||
| 出版者 | Public Library of Science | |||||
| 言語 | en | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1371/journal.pone.0002668 | |||||
| ISSN | ||||||
| 収録物識別子タイプ | EISSN | |||||
| 収録物識別子 | 1932-6203 | |||||
| 著作権関連情報 | ||||||
| 権利情報 | Copyright (c) 2008 Shakèd et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 査読の有無 | ||||||
| 値 | yes | |||||
| 連携ID | ||||||
| 値 | 660 | |||||
