Abstract

Sufficient tissue oxygenation is required for regular brain function; thus oxygen supply must be tightly regulated to avoid hypoxia and irreversible cell damage. If hypoxia occurs the transcription factor complex hypoxia-inducible factor (HIF) will accumulate and coordinate adaptation of cells to hypoxia. However, even under atmospheric O2 conditions stabilized HIF-2α protein was found in brains of adult mice. Mice with a neuro-specific knockout of Hif-2α showed a reduction of pyramidal neurons in the retrosplenial cortex (RSC), a brain region responsible for a range of cognitive functions, including memory and navigation. Accordingly, behavioral studies showed disturbed cognitive abilities in these mice. In search of the underlying mechanisms for the specific loss of pyramidal cells in the RSC, we found deficits in migration in neural stem cells from Hif-2α knockout mice due to altered expression patterns of genes highly associated with neuronal migration and positioning.

Details

Title
Hypoxia-inducible factor-2α is crucial for proper brain development
Author
Kleszka Kira 1 ; Leu Tristan 1 ; Quinting Theresa 1 ; Jastrow Holger 2 ; Pechlivanis Sonali 3 ; Fandrey Joachim 1 ; Schreiber Timm 4 

 University Duisburg-Essen, Institute of Physiology, Essen, Germany (GRID:grid.5718.b) (ISNI:0000 0001 2187 5445) 
 Essen University Hospital, Institute of Anatomy and Institute for Experimental Immunology and Imaging, Imaging Centre Essen, Electron Microscopy Unit, Essen, Germany (GRID:grid.410718.b) (ISNI:0000 0001 0262 7331) 
 University Hospital of Essen, University Duisburg-Essen, Institute for Medical Informatics, Biometry and Epidemiology, Essen, Germany (GRID:grid.410718.b) 
 University Duisburg-Essen, Institute of Physiology, Essen, Germany (GRID:grid.5718.b) (ISNI:0000 0001 2187 5445); University of Witten/Herdecke, Department of Physiology, Pathophysiology and Toxicology and Center for Biomedical Education and Research (ZBAF), Witten, Germany (GRID:grid.412581.b) (ISNI:0000 0000 9024 6397) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2471541353
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.