PUBLICATION
Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish
- Authors
- Antón-Galindo, E., Dalla Vecchia, E., Orlandi, J.G., Castro, G., Gualda, E.J., Young, A.M.J., Guasch-Piqueras, M., Arenas, C., Herrera-Úbeda, C., Garcia-Fernàndez, J., Aguado, F., Loza-Alvarez, P., Cormand, B., Norton, W.H.J., Fernàndez-Castillo, N.
- ID
- ZDB-PUB-220505-2
- Date
- 2022
- Source
- Molecular psychiatry 27(9): 3739-3748 (Journal)
- Registered Authors
- Gualda, Emilio, Loza-Alvarez, Pablo, Norton, Will
- Keywords
- none
- MeSH Terms
-
- 14-3-3 Proteins*/genetics
- Animals
- Autism Spectrum Disorder/genetics
- Autism Spectrum Disorder/physiopathology
- Autistic Disorder/genetics
- Autistic Disorder/physiopathology
- Brain*/metabolism
- Brain*/physiopathology
- Humans
- Neurodevelopmental Disorders/genetics
- Neurodevelopmental Disorders/physiopathology
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- PubMed
- 35501409 Full text @ Mol. Psychiatry
Citation
Antón-Galindo, E., Dalla Vecchia, E., Orlandi, J.G., Castro, G., Gualda, E.J., Young, A.M.J., Guasch-Piqueras, M., Arenas, C., Herrera-Úbeda, C., Garcia-Fernàndez, J., Aguado, F., Loza-Alvarez, P., Cormand, B., Norton, W.H.J., Fernàndez-Castillo, N. (2022) Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish. Molecular psychiatry. 27(9):3739-3748.
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. We then performed whole-brain imaging in wild-type and ywhaz CRISPR/Cas9 knockout (KO) larvae and found altered neuronal activity and connectivity in the hindbrain. Adult ywhaz KO fish display decreased levels of monoamines in the hindbrain and freeze when exposed to novel stimuli, a phenotype that can be reversed with drugs that target monoamine neurotransmission. These findings suggest an important role for ywhaz in establishing neuronal connectivity during development and modulating both neurotransmission and behaviour in adults.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping