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Cell Rep. 2014 Aug 7;8(3):665-70. doi: 10.1016/j.celrep.2014.06.057. Epub 2014 Jul 31.

CtBPs sense microenvironmental oxygen levels to regulate neural stem cell state.

Author information

1
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, Sweden.
2
Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
3
Howard Hughes Medical Institute School of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
4
Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden. Electronic address: ola.hermanson@ki.se.
5
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, Sweden. Electronic address: ana.teixeira@ki.se.

Abstract

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.

PMID:
25088415
DOI:
10.1016/j.celrep.2014.06.057
[Indexed for MEDLINE]
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