Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783440567584161792 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6672001 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT domingueziturzanuria theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT loadrianc theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT shahdisha theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT armendarizmarcelo theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT vannellianna theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT mercaldovalentina theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT truselmassimo theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT likawan theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT gastaldodenise theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT santosanarita theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT callaertsveghzsuzsanna theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT dhoogerudi theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT mamelimanuel theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT vanderlindenannemie theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT smitaugustb theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT achseltilmann theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT bagniclaudia theautismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT domingueziturzanuria autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT loadrianc autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT shahdisha autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT armendarizmarcelo autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT vannellianna autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT mercaldovalentina autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT truselmassimo autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT likawan autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT gastaldodenise autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT santosanarita autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT callaertsveghzsuzsanna autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT dhoogerudi autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT mamelimanuel autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT vanderlindenannemie autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT smitaugustb autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT achseltilmann autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour AT bagniclaudia autismandschizophreniaassociatedproteincyfip1regulatesbilateralbrainconnectivityandbehaviour |