{
  "abstract": "Dynamic changes in physiological oxygen levels are crucial for proper cortical brain development. In this context, oxygen is important not only for its role in energy metabolism but also as a signaling molecule. While much is already known about its most prominent signaling factor hypoxia-inducible factor (HIF)-1α, little is known about its functionally similar isoform HIF-2α during cortical development. Therefore, we utilized HIF-2α conditional knock-out mice (Emx1 and Nestin driven), which were kept under maternal hypoxia (10% pO2), physioxia (21% pO2), or hyperoxia (75% pO2) starting at E14.5 for 48 h and analyzed their cortical development by immunohistochemistry at E16.5. The analysis of newborn neurons (BrdU+) and cortical layer IV (Tbr1+), V (Ctip2+), and upper layer neurons (Satb2+) revealed clear effects of oxygen, with hyperoxia particularly increasing the number of Ctip2+/Tbr1- layer V neurons in E16.5 fetuses. However, neither the number of newborn neurons nor the number of layer-specific neurons was affected by HIF-2α CKO. Similarly, oxygen-related effects on neural stem cells (NSCs) and neuroprogenitor cells were not mediated by HIF-2α in E16.5 fetuses. Contributing, in vitro expansion and stem cell maintenance of NSCs were accelerated by physioxia (3% pO2) compared to hyperoxia (21% pO2), without involvement of HIF-2α under either condition. In conclusion, oxygen modulates cortical development, but HIF-2α does not mediate these effects. Thus, oxygen-related changes in neurogenesis and cortical morphology appear to be regulated via HIF-2α-independent mechanisms.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, University of Rostock, Rostock, Mecklenburg-Western Pomerania, Germany",
    "German Centre for Neurodegenerative Diseases (DZNE) Rostock-Greifswald, Rostock, Mecklenburg-Western Pomerania, Germany"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jennifer Lanto"
    },
    {
      "affs": [
        1
      ],
      "name": "Laura Rohmann"
    },
    {
      "name": "Tim Theege"
    },
    {
      "name": "Valeriia Abramenko"
    },
    {
      "name": "Lisa Große"
    },
    {
      "name": "Andreas Madlener"
    },
    {
      "name": "Julia Anna Elisabeth Neitzel"
    },
    {
      "name": "Alexander Storch"
    },
    {
      "name": "Franz Markert"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cgwxebamcx05x.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0359507",
  "fulltext_url": null,
  "id": "cgwxebamcx05x",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0359507",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2806|Neurogenesis and neuroplasticity mechanisms"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons"
    ],
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      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Stem cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Stem cells/Neural stem cells/Neural stem cell neurogenesis"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Hypoxia"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Organism development/Organogenesis/Brain development"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neural stem cells/Neural stem cell neurogenesis"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurogenesis/Cortical neurogenesis"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurogenesis/Neural stem cell neurogenesis"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Developmental neuroscience/Neural stem cells/Neural stem cell neurogenesis"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Developmental neuroscience/Neurogenesis/Cortical neurogenesis"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Developmental neuroscience/Neurogenesis/Neural stem cell neurogenesis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Hyperoxia"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical elements/Oxygen"
    ]
  ],
  "openalex": "W7203908234",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0359507&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-14",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/cgwxebamcx05x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:23Z",
      "native_id": "10.1371/journal.pone.0359507",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0359507"
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Hypoxia-inducible factor 2α does not regulate cortical brain development",
  "title_text": "Hypoxia-inducible factor 2α does not regulate cortical brain development",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:23Z",
  "url": "https://research.draconitic.com/paper/cgwxebamcx05x",
  "venue": "PLOS One",
  "versions": []
}