Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish

Abstract

Genetic variants in YWHAZ contribute to psychiatric disorders such as autism spectrum disorder and schizophrenia, and have been related to an impaired neurodevelopment in humans and mice. Here, we have used zebrafish to investigate the mechanisms by which YWHAZ contributes to neurodevelopmental disorders. We observed that ywhaz expression was pan-neuronal during developmental stages and restricted to Purkinje cells in the adult cerebellum, cells that are described to be reduced in number and size in autistic patients.

GCaMP6s albino zebrafish embryos were generated by the National Institute of Genetics (Japan) and obtained from Dr. Matt Parker from the University of Portsmouth, UK. The Tg(aldoca:gap43-Venus) line was obtained from Masahiko Hibi from the Bioscience and Biotechnology Center of Nagoya University, Japan. Tg(olig2:egfp)vu12 brains were obtained from the Center for Developmental Biology, UMR 5547 CNRS, Toulouse, France. 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’ (2017-SGR-738), ICREA Academia 2021, and the European Union H2020 Program [H2020/2014-2020] under grant agreements n° 667302 (CoCA) and Eat2beNICE (728018). E.A-G was supported by the Ministerio de Economía y Competitividad (Spanish Government) and the EU H2020 program (Eat2beNICE-728018). G.C., E.G. and P.L-A acknowledge financial support from the Spanish Ministerio de Economía y Competitividad (MINECO) through the “Severo Ochoa” program for Centres of Excellence in R&D CEX2019-000910-S), MINECO/FEDER Ramon y Cajal program (RYC-2015-17935); Laserlab-Europe EU-H2020 GA no. 871124, Fundació Privada Cellex, Fundación Mig-Puig and from the Generalitat de Catalunya through the CERCA program. F.A. acknowledges financial support from the Spanish ‘Ministerio de Ciencia, Innovación y Universidades’ (PID2019-107738RB-I00, MICINN/FEDER) and SGR (2017SGR1255).

Postprint (author's final draft)