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The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour

Copy-number variants of the CYFIP1 gene in humans have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), two neuropsychiatric disorders characterized by defects in brain connectivity. Here, we show that CYFIP1 plays an important role in brain functional connectivity and callosa...

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Autores principales: Domínguez-Iturza, Nuria, Lo, Adrian C., Shah, Disha, Armendáriz, Marcelo, Vannelli, Anna, Mercaldo, Valentina, Trusel, Massimo, Li, Ka Wan, Gastaldo, Denise, Santos, Ana Rita, Callaerts-Vegh, Zsuzsanna, D’Hooge, Rudi, Mameli, Manuel, Van der Linden, Annemie, Smit, August B., Achsel, Tilmann, Bagni, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672001/
https://www.ncbi.nlm.nih.gov/pubmed/31371726
http://dx.doi.org/10.1038/s41467-019-11203-y
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author Domínguez-Iturza, Nuria
Lo, Adrian C.
Shah, Disha
Armendáriz, Marcelo
Vannelli, Anna
Mercaldo, Valentina
Trusel, Massimo
Li, Ka Wan
Gastaldo, Denise
Santos, Ana Rita
Callaerts-Vegh, Zsuzsanna
D’Hooge, Rudi
Mameli, Manuel
Van der Linden, Annemie
Smit, August B.
Achsel, Tilmann
Bagni, Claudia
author_facet Domínguez-Iturza, Nuria
Lo, Adrian C.
Shah, Disha
Armendáriz, Marcelo
Vannelli, Anna
Mercaldo, Valentina
Trusel, Massimo
Li, Ka Wan
Gastaldo, Denise
Santos, Ana Rita
Callaerts-Vegh, Zsuzsanna
D’Hooge, Rudi
Mameli, Manuel
Van der Linden, Annemie
Smit, August B.
Achsel, Tilmann
Bagni, Claudia
author_sort Domínguez-Iturza, Nuria
collection PubMed
description Copy-number variants of the CYFIP1 gene in humans have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), two neuropsychiatric disorders characterized by defects in brain connectivity. Here, we show that CYFIP1 plays an important role in brain functional connectivity and callosal functions. We find that Cyfip1-heterozygous mice have reduced functional connectivity and defects in white matter architecture, similar to phenotypes found in patients with ASD, SCZ and other neuropsychiatric disorders. Cyfip1-deficient mice also present decreased myelination in the callosal axons, altered presynaptic function, and impaired bilateral connectivity. Finally, Cyfip1 deficiency leads to abnormalities in motor coordination, sensorimotor gating and sensory perception, which are also known neuropsychiatric disorder-related symptoms. These results show that Cyfip1 haploinsufficiency compromises brain connectivity and function, which might explain its genetic association to neuropsychiatric disorders.
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spelling pubmed-66720012019-08-02 The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour Domínguez-Iturza, Nuria Lo, Adrian C. Shah, Disha Armendáriz, Marcelo Vannelli, Anna Mercaldo, Valentina Trusel, Massimo Li, Ka Wan Gastaldo, Denise Santos, Ana Rita Callaerts-Vegh, Zsuzsanna D’Hooge, Rudi Mameli, Manuel Van der Linden, Annemie Smit, August B. Achsel, Tilmann Bagni, Claudia Nat Commun Article Copy-number variants of the CYFIP1 gene in humans have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), two neuropsychiatric disorders characterized by defects in brain connectivity. Here, we show that CYFIP1 plays an important role in brain functional connectivity and callosal functions. We find that Cyfip1-heterozygous mice have reduced functional connectivity and defects in white matter architecture, similar to phenotypes found in patients with ASD, SCZ and other neuropsychiatric disorders. Cyfip1-deficient mice also present decreased myelination in the callosal axons, altered presynaptic function, and impaired bilateral connectivity. Finally, Cyfip1 deficiency leads to abnormalities in motor coordination, sensorimotor gating and sensory perception, which are also known neuropsychiatric disorder-related symptoms. These results show that Cyfip1 haploinsufficiency compromises brain connectivity and function, which might explain its genetic association to neuropsychiatric disorders. Nature Publishing Group UK 2019-08-01 /pmc/articles/PMC6672001/ /pubmed/31371726 http://dx.doi.org/10.1038/s41467-019-11203-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Domínguez-Iturza, Nuria
Lo, Adrian C.
Shah, Disha
Armendáriz, Marcelo
Vannelli, Anna
Mercaldo, Valentina
Trusel, Massimo
Li, Ka Wan
Gastaldo, Denise
Santos, Ana Rita
Callaerts-Vegh, Zsuzsanna
D’Hooge, Rudi
Mameli, Manuel
Van der Linden, Annemie
Smit, August B.
Achsel, Tilmann
Bagni, Claudia
The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour
title The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour
title_full The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour
title_fullStr The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour
title_full_unstemmed The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour
title_short The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour
title_sort autism- and schizophrenia-associated protein cyfip1 regulates bilateral brain connectivity and behaviour
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672001/
https://www.ncbi.nlm.nih.gov/pubmed/31371726
http://dx.doi.org/10.1038/s41467-019-11203-y
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