CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell State

Bone morphogenetic proteins (BMPs) secreted by the dorsal neural tube and overlying ectoderm are key signals for the specification of the roof plate and dorsal interneuron populations. However, the signals that confer nonneurogenic character to the roof plate region are largely unknown. We report th...

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Main Authors:	José M. Dias, Shirin Ilkhanizadeh, Esra Karaca, Joshua K. Duckworth, Vanessa Lundin, Michael G. Rosenfeld, Johan Ericson, Ola Hermanson, Ana I. Teixeira
Format:	Article
Language:	English
Published:	Elsevier 2014-08-01
Series:	Cell Reports
Online Access:	http://www.sciencedirect.com/science/article/pii/S2211124714005592

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spelling	doaj-eb74307279ea4cefb609b8cb11cd77b82020-11-24T21:47:22ZengElsevierCell Reports2211-12472014-08-018366567010.1016/j.celrep.2014.06.057CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell StateJosé M. Dias0Shirin Ilkhanizadeh1Esra Karaca2Joshua K. Duckworth3Vanessa Lundin4Michael G. Rosenfeld5Johan Ericson6Ola Hermanson7Ana I. Teixeira8Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, SwedenDepartment of Neuroscience, Karolinska Institutet, Stockholm, 171 77, SwedenDepartment of Neuroscience, Karolinska Institutet, Stockholm, 171 77, SwedenDepartment of Neuroscience, Karolinska Institutet, Stockholm, 171 77, SwedenDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, SwedenHoward Hughes Medical Institute School of Medicine, University of California, San Diego, San Diego, CA 92093, USADepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, SwedenDepartment of Neuroscience, Karolinska Institutet, Stockholm, 171 77, SwedenDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, SwedenBone morphogenetic proteins (BMPs) secreted by the dorsal neural tube and overlying ectoderm are key signals for the specification of the roof plate and dorsal interneuron populations. However, the signals that confer nonneurogenic character to the roof plate region are largely unknown. We report that the roof plate region shows elevated oxygen levels compared to neurogenic regions of the neural tube. These high oxygen levels are required for the expression of the antineuronal transcription factor Hes1 in the roof plate region. The transcriptional corepressor CtBP is a critical mediator of the oxygen-sensing response. High oxygen promotes a decrease in the CtBP occupancy of the promoter of Hes1. Furthermore, under conditions of high oxygen and BMP, CtBP associates with HES1 and represses neurogenesis. We propose that CtBP integrates signals originating from microenvironmental levels of oxygen and BMP to confer nonneurogenic character to the roof plate region.http://www.sciencedirect.com/science/article/pii/S2211124714005592
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	José M. Dias Shirin Ilkhanizadeh Esra Karaca Joshua K. Duckworth Vanessa Lundin Michael G. Rosenfeld Johan Ericson Ola Hermanson Ana I. Teixeira
spellingShingle	José M. Dias Shirin Ilkhanizadeh Esra Karaca Joshua K. Duckworth Vanessa Lundin Michael G. Rosenfeld Johan Ericson Ola Hermanson Ana I. Teixeira CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell State Cell Reports
author_facet	José M. Dias Shirin Ilkhanizadeh Esra Karaca Joshua K. Duckworth Vanessa Lundin Michael G. Rosenfeld Johan Ericson Ola Hermanson Ana I. Teixeira
author_sort	José M. Dias
title	CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell State
title_short	CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell State
title_full	CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell State
title_fullStr	CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell State
title_full_unstemmed	CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell State
title_sort	ctbps sense microenvironmental oxygen levels to regulate neural stem cell state
publisher	Elsevier
series	Cell Reports
issn	2211-1247
publishDate	2014-08-01
description	Bone morphogenetic proteins (BMPs) secreted by the dorsal neural tube and overlying ectoderm are key signals for the specification of the roof plate and dorsal interneuron populations. However, the signals that confer nonneurogenic character to the roof plate region are largely unknown. We report that the roof plate region shows elevated oxygen levels compared to neurogenic regions of the neural tube. These high oxygen levels are required for the expression of the antineuronal transcription factor Hes1 in the roof plate region. The transcriptional corepressor CtBP is a critical mediator of the oxygen-sensing response. High oxygen promotes a decrease in the CtBP occupancy of the promoter of Hes1. Furthermore, under conditions of high oxygen and BMP, CtBP associates with HES1 and represses neurogenesis. We propose that CtBP integrates signals originating from microenvironmental levels of oxygen and BMP to confer nonneurogenic character to the roof plate region.
url	http://www.sciencedirect.com/science/article/pii/S2211124714005592
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CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell State

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