title: CtBPs sense microenvironmental oxygen levels to regulate neural stem cell state.
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.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors.forename: José M
authors.initials: JM
authors.lastname: Dias
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors.forename: Shirin
authors.initials: S
authors.lastname: Ilkhanizadeh
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors.forename: Esra
authors.initials: E
authors.lastname: Karaca
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors.forename: Joshua K
authors.initials: JK
authors.lastname: Duckworth
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lundin
authors.affiliation: Howard Hughes Medical Institute School of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ericson
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden. Electronic address: ola.hermanson@ki.se.
authors.forename: Ola
authors.initials: O
authors.lastname: Hermanson
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, Sweden. Electronic address: ana.teixeira@ki.se.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002642:Chick Embryo; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D054259:Neural Tube / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D010100:Oxygen / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D055153:Stem Cell Niche; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D010100:Oxygen; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C119945:Ctbp1 protein, rat; C486016:Ctbp2 protein, rat; C489735:Hes1 protein, rat