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Pleiotropic contribution of rbfox1 to psychiatric and neurodevelopmental phenotypes in two zebrafish models

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dc.contributor.author Antón Galindo, Ester
dc.contributor.author Adel, Maja R.
dc.contributor.author García González, Judit
dc.contributor.author Leggieri, Adele
dc.contributor.author López Blanch, Laura
dc.contributor.author Irimia Martínez, Manuel
dc.contributor.author Norton, William H. J.
dc.contributor.author Brennan, Caroline H.
dc.contributor.author Fernàndez-Castillo, Noèlia
dc.contributor.author Cormand, Bru
dc.date.accessioned 2024-07-23T12:40:34Z
dc.date.available 2024-07-23T12:40:34Z
dc.date.issued 2024
dc.identifier.citation Antón-Galindo E, Adel MR, García-González J, Leggieri A, López-Blanch L, Irimia M, et al. Pleiotropic contribution of rbfox1 to psychiatric and neurodevelopmental phenotypes in two zebrafish models. Transl Psychiatry. 2024 Feb 19;14(1):99. DOI: 10.1038/s41398-024-02801-6
dc.identifier.issn 2158-3188
dc.identifier.uri http://hdl.handle.net/10230/60815
dc.description.abstract RBFOX1 is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants in RBFOX1 have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects of RBFOX1 are not yet understood. Here we found that, in zebrafish, rbfox1 is expressed in spinal cord, mid- and hindbrain during developmental stages. In adults, expression is restricted to specific areas of the brain, including telencephalic and diencephalic regions with an important role in receiving and processing sensory information and in directing behaviour. To investigate the contribution of rbfox1 to behaviour, we used rbfox1sa15940, a zebrafish mutant line with TL background. We found that rbfox1sa15940 mutants present hyperactivity, thigmotaxis, decreased freezing behaviour and altered social behaviour. We repeated these behavioural tests in a second rbfox1 mutant line with a different genetic background (TU), rbfox1del19, and found that rbfox1 deficiency affects behaviour similarly in this line, although there were some differences. rbfox1del19 mutants present similar thigmotaxis, but stronger alterations in social behaviour and lower levels of hyperactivity than rbfox1sa15940 fish. Taken together, these results suggest that mutations in rbfox1 lead to multiple behavioural changes in zebrafish that might be modulated by environmental, epigenetic and genetic background effects, and that resemble phenotypic alterations present in Rbfox1-deficient mice and in patients with different psychiatric conditions. Our study, thus, highlights the evolutionary conservation of rbfox1 function in behaviour and paves the way to further investigate the mechanisms underlying rbfox1 pleiotropy on the onset of neurodevelopmental and psychiatric disorders.
dc.description.sponsorship Major financial support for this research was received by BC from the Spanish ‘Ministerio de Ciencia, Innovación y Universidades’ (RTI2018-100968-B-100, PID2021-1277760B-I100), the ‘Ministerio de Sanidad, Servicios Sociales e Igualdad/Plan Nacional Sobre Drogas’ (PNSD-2017I050 and PNSD-2020I042), ‘Generalitat de Catalunya/AGAUR’ (2021-SGR-01093), ICREA Academia 2021, ‘Fundació La Marató de TV3’ (202218-31) and the European Union H2020 Program [H2020/2014-2020] under grant agreements n° 667302 (CoCA) and Eat2beNICE (728018), and received by CHB from the NIH (USA) (5 U01 DA044400-05). E.A-G was supported by the Ministerio de Economía y Competitividad (Spanish Government), the EU H2020 program (Eat2beNICE-728018) and a Margarita Salas postdoctoral grant. M.R.A. was supported by a doctoral scholarship of the ‘Studienstiftung des Deutschen Volkes’. J.G-G. was supported by the Queen Mary Principal’s Research Studentship in the School of Biological and Chemical Sciences.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Transl Psychiatry. 2024 Feb 19;14(1):99
dc.rights © The Author(s) 2024. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Pleiotropic contribution of rbfox1 to psychiatric and neurodevelopmental phenotypes in two zebrafish models
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41398-024-02801-6
dc.subject.keyword Genetics
dc.subject.keyword Medical genetics
dc.subject.keyword Molecular neuroscience
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/667302
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-100968-B-100
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-1277760B-I100
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/728018
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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