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NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome

The nuclear receptor NR2F1 acts as a strong transcriptional regulator in embryonic and postnatal neural cells. In humans, mutations in the NR2F1 gene cause Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), a rare neurodevelopmental disorder characterized by multiple clinical features including...

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Autores principales: Bonzano, Sara, Dallorto, Eleonora, Molineris, Ivan, Michelon, Filippo, Crisci, Isabella, Gambarotta, Giovanna, Neri, Francesco, Oliviero, Salvatore, Beckervordersandforth, Ruth, Lie, Dieter Chichung, Peretto, Paolo, Bovetti, Serena, Studer, Michèle, Marchis, Silvia De
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10309583/
https://www.ncbi.nlm.nih.gov/pubmed/37260288
http://dx.doi.org/10.1242/dmm.049854
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author Bonzano, Sara
Dallorto, Eleonora
Molineris, Ivan
Michelon, Filippo
Crisci, Isabella
Gambarotta, Giovanna
Neri, Francesco
Oliviero, Salvatore
Beckervordersandforth, Ruth
Lie, Dieter Chichung
Peretto, Paolo
Bovetti, Serena
Studer, Michèle
Marchis, Silvia De
author_facet Bonzano, Sara
Dallorto, Eleonora
Molineris, Ivan
Michelon, Filippo
Crisci, Isabella
Gambarotta, Giovanna
Neri, Francesco
Oliviero, Salvatore
Beckervordersandforth, Ruth
Lie, Dieter Chichung
Peretto, Paolo
Bovetti, Serena
Studer, Michèle
Marchis, Silvia De
author_sort Bonzano, Sara
collection PubMed
description The nuclear receptor NR2F1 acts as a strong transcriptional regulator in embryonic and postnatal neural cells. In humans, mutations in the NR2F1 gene cause Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), a rare neurodevelopmental disorder characterized by multiple clinical features including vision impairment, intellectual disability and autistic traits. In this study, we identified, by genome-wide and in silico analyses, a set of nuclear-encoded mitochondrial genes as potential genomic targets under direct NR2F1 transcriptional control in neurons. By combining mouse genetic, 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, the genesis, survival and functional integration of which are impaired. Importantly, we also found dysregulation of several nuclear-encoded mitochondrial genes and downregulation of key mitochondrial proteins in the brain of Nr2f1-heterozygous mice, a validated BBSOAS model. Our data point to an active role for NR2F1 in the mitochondrial gene expression regulatory network in neurons and support the involvement of mitochondrial dysfunction in BBSOAS pathogenesis.
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spelling pubmed-103095832023-06-30 NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome Bonzano, Sara Dallorto, Eleonora Molineris, Ivan Michelon, Filippo Crisci, Isabella Gambarotta, Giovanna Neri, Francesco Oliviero, Salvatore Beckervordersandforth, Ruth Lie, Dieter Chichung Peretto, Paolo Bovetti, Serena Studer, Michèle Marchis, Silvia De Dis Model Mech Research Article The nuclear receptor NR2F1 acts as a strong transcriptional regulator in embryonic and postnatal neural cells. In humans, mutations in the NR2F1 gene cause Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), a rare neurodevelopmental disorder characterized by multiple clinical features including vision impairment, intellectual disability and autistic traits. In this study, we identified, by genome-wide and in silico analyses, a set of nuclear-encoded mitochondrial genes as potential genomic targets under direct NR2F1 transcriptional control in neurons. By combining mouse genetic, 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, the genesis, survival and functional integration of which are impaired. Importantly, we also found dysregulation of several nuclear-encoded mitochondrial genes and downregulation of key mitochondrial proteins in the brain of Nr2f1-heterozygous mice, a validated BBSOAS model. Our data point to an active role for NR2F1 in the mitochondrial gene expression regulatory network in neurons and support the involvement of mitochondrial dysfunction in BBSOAS pathogenesis. The Company of Biologists Ltd 2023-06-26 /pmc/articles/PMC10309583/ /pubmed/37260288 http://dx.doi.org/10.1242/dmm.049854 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Bonzano, Sara
Dallorto, Eleonora
Molineris, Ivan
Michelon, Filippo
Crisci, Isabella
Gambarotta, Giovanna
Neri, Francesco
Oliviero, Salvatore
Beckervordersandforth, Ruth
Lie, Dieter Chichung
Peretto, Paolo
Bovetti, Serena
Studer, Michèle
Marchis, Silvia De
NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome
title NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome
title_full NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome
title_fullStr NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome
title_full_unstemmed NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome
title_short NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome
title_sort nr2f1 shapes mitochondria in the mouse brain, providing new insights into bosch-boonstra-schaaf optic atrophy syndrome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10309583/
https://www.ncbi.nlm.nih.gov/pubmed/37260288
http://dx.doi.org/10.1242/dmm.049854
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