{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:52:37Z","timestamp":1792788757110,"version":"4.5.0"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universit\u00e4t Rostock Professorinnenprogramm III","id":[{"id":"https:\/\/ror.org\/03zdwsf69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"CRC 1270 \u2018Electrically Active Implants\u2019","award":["299150580"],"award-info":[{"award-number":["299150580"]}]},{"name":"Europ\u00e4ischen Fonds f\u00fcr regionale Entwicklung","award":["GHS-19-0011"],"award-info":[{"award-number":["GHS-19-0011"]}]},{"name":"Europ\u00e4ischen Fonds f\u00fcr regionale Entwicklung","award":["GHS-19 0012"],"award-info":[{"award-number":["GHS-19 0012"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    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)-1\u03b1, little is known about its functionally similar isoform HIF-2\u03b1 during cortical development. Therefore, we utilized HIF-2\u03b1 conditional knock-out mice (Emx1 and Nestin driven), which were kept under maternal hypoxia (10% pO\n                    <jats:sub>2<\/jats:sub>\n                    ), physioxia (21% pO\n                    <jats:sub>2<\/jats:sub>\n                    ), or hyperoxia (75% pO\n                    <jats:sub>2<\/jats:sub>\n                    ) starting at E14.5 for 48 h and analyzed their cortical development by immunohistochemistry at E16.5. The analysis of newborn neurons (BrdU\n                    <jats:sup>+<\/jats:sup>\n                    ) and cortical layer IV (Tbr1\n                    <jats:sup>+<\/jats:sup>\n                    ), V (Ctip2\n                    <jats:sup>+<\/jats:sup>\n                    ), and upper layer neurons (Satb2\n                    <jats:sup>+<\/jats:sup>\n                    ) revealed clear effects of oxygen, with hyperoxia particularly increasing the number of Ctip2\n                    <jats:sup>+<\/jats:sup>\n                    \/Tbr1\n                    <jats:sup>-<\/jats:sup>\n                    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-2\u03b1 CKO. Similarly, oxygen-related effects on neural stem cells (NSCs) and neuroprogenitor cells were not mediated by HIF-2\u03b1 in E16.5 fetuses. Contributing,\n                    <jats:italic>in vitro<\/jats:italic>\n                    expansion and stem cell maintenance of NSCs were accelerated by physioxia (3% pO\n                    <jats:sub>2<\/jats:sub>\n                    ) compared to hyperoxia (21% pO\n                    <jats:sub>2<\/jats:sub>\n                    ), without involvement of HIF-2\u03b1 under either condition. In conclusion, oxygen modulates cortical development, but HIF-2\u03b1 does not mediate these effects. Thus, oxygen-related changes in neurogenesis and cortical morphology appear to be regulated via HIF-2\u03b1-independent mechanisms.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0359507","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:29:39Z","timestamp":1791998979000},"page":"e0359507","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypoxia-inducible factor 2\u03b1 does not regulate cortical brain development"],"prefix":"10.1371","volume":"21","author":[{"given":"Jennifer","family":"Lanto","sequence":"first","affiliation":[{"name":"University of Rostock","place":["Rostock, Mecklenburg-Western Pomerania, Germany"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rohmann","sequence":"additional","affiliation":[{"name":"University of Rostock","place":["Rostock, Mecklenburg-Western Pomerania, Germany"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Theege","sequence":"additional","affiliation":[{"name":"University of Rostock","place":["Rostock, Mecklenburg-Western Pomerania, Germany"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriia","family":"Abramenko","sequence":"additional","affiliation":[{"name":"University of Rostock","place":["Rostock, Mecklenburg-Western Pomerania, Germany"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Gro\u00dfe","sequence":"additional","affiliation":[{"name":"University of Rostock","place":["Rostock, Mecklenburg-Western Pomerania, Germany"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Madlener","sequence":"additional","affiliation":[{"name":"University of Rostock","place":["Rostock, Mecklenburg-Western Pomerania, Germany"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Anna Elisabeth","family":"Neitzel","sequence":"additional","affiliation":[{"name":"University of Rostock","place":["Rostock, Mecklenburg-Western Pomerania, Germany"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Storch","sequence":"additional","affiliation":[{"name":"University of Rostock","place":["Rostock, Mecklenburg-Western Pomerania, Germany"],"department":["Department of Neurology"]},{"name":"German Centre for Neurodegenerative Diseases (DZNE) Rostock-Greifswald","place":["Rostock, Mecklenburg-Western Pomerania, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6502-2567","authenticated-orcid":true,"given":"Franz","family":"Markert","sequence":"additional","affiliation":[{"name":"University of Rostock","place":["Rostock, Mecklenburg-Western Pomerania, Germany"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"issue":"4","key":"pone.0359507.ref001","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.braindev.2011.07.006","article-title":"Systemic hypoxia differentially affects neurogenesis during early mouse brain maturation","volume":"34","author":"C Schneider","year":"2012","journal-title":"Brain Dev"},{"issue":"9","key":"pone.0359507.ref002","doi-asserted-by":"crossref","first-page":"924","DOI":"10.15252\/embj.201592372","article-title":"Relief of hypoxia by angiogenesis promotes neural stem cell 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