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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jun 09, 2023 |
Title |
Nr2f1 shapes mitochondria in the mouse brain unraveling novel insights into the neurodevelopmental disorder BBSOAS |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The nuclear receptor Nr2f1 acts as a strong transcriptional regulator in embryonic and postnatal neural cells. In humans, its mutations cause the Bosch-Boonstra-Schaaf optic atrophy-intellectual syndrome (BBSOAS), a rare neurodevelopmental disorder characterized by multiple clinical features including optic nerve atrophy, intellectual disability, and autistic traits. In this study, by genome-wide and in silico analyses we identified a wide set of nuclear-encoded mitochondrial genes as potential genomic targets under direct Nr2f1 transcriptional control in neurons. By combining mouse genetics, neuroanatomical and imaging approaches we demonstrated that conditional Nr2f1 loss-of-function within the adult mouse hippocampal neurogenic niche results in a reduced mitochondrial mass associated with mitochondrial fragmentation and downregulation of key mitochondrial proteins in newborn neurons, whose functional integration and survival are impaired. Importantly, we also found dysregulation of several mitochondrial genes and downregulation in levels of key mitochondrial proteins in the brain of mice heterozygous for Nr2f1, a validated BBSOAS model. Our data point to an active role of Nr2f1 in the mitochondrial gene expression regulatory network in neurons and support the involvement of mitochondrial dysfunction in BBSOAS pathogenesis.
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Overall design |
3 samples
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Contributor(s) |
Bonzano S, Dallorto E, Molineris I, Michelon F, Crisci I, Gambarotta G, Neri F, Oliviero S, Beckervordersandforth R, Lie DC, Peretto P, Bovetti S, Studer M, De Marchis S |
Citation(s) |
37260288 |
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Submission date |
Mar 30, 2023 |
Last update date |
Sep 11, 2023 |
Contact name |
Ivan Molineris |
Organization name |
University of Turin
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Department |
Life Science and System Biology
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Lab |
Epigenetics Labs
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Street address |
Via Nizza 52
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City |
Torino |
State/province |
TO |
ZIP/Postal code |
10126 |
Country |
Italy |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (3) |
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Relations |
BioProject |
PRJNA950374 |
Supplementary file |
Size |
Download |
File type/resource |
GSE228566_RAW.tar |
1020.0 Kb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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