SUMMARY
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 used zebrafish to further understand the mechanisms by which YWHAZ contributes to neurodevelopmental disorders. We observed that ywhaz expression was panneuronal during developmental stages and restricted to Purkinje cells in the adult cerebellum, cells that are described to be reduced in number 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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Lead contact: Ester Antón Galindo, eantongalindo{at}ub.edu
Material and Methods and Results sections have been updated to be more understandable. All the figures have been revised and reordered. Supplementary files updated.
