PUBLICATION
High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways
- Authors
- Weinschutz Mendes, H., Neelakantan, U., Liu, Y., Fitzpatrick, S.E., Chen, T., Wu, W., Pruitt, A., Jin, D.S., Jamadagni, P., Carlson, M., Lacadie, C.M., Enriquez, K.D., Li, N., Zhao, D., Ijaz, S., Sakai, C., Szi, C., Rooney, B., Ghosh, M., Nwabudike, I., Gorodezky, A., Chowdhury, S., Zaheer, M., McLaughlin, S., Fernandez, J.M., Wu, J., Eilbott, J.A., Vander Wyk, B., Rihel, J., Papademetris, X., Wang, Z., Hoffman, E.J.
- ID
- ZDB-PUB-230319-34
- Date
- 2023
- Source
- Cell Reports 42: 112243112243 (Journal)
- Registered Authors
- Chen, Tianying, Fitzpatrick, Sarah E., Ghosh, Marcus, Hoffman, Ellen, Rihel, Jason
- Keywords
- CP: Neuroscience, autism spectrum disorder, dopaminergic neurons, genetics, microglia, neurodevelopment, zebrafish
- Datasets
- GEO:GSE205578
- MeSH Terms
-
- Animals
- Autism Spectrum Disorder*/genetics
- Autistic Disorder*/genetics
- Brain
- Brain Mapping
- Zebrafish/genetics
- PubMed
- 36933215 Full text @ Cell Rep.
Citation
Weinschutz Mendes, H., Neelakantan, U., Liu, Y., Fitzpatrick, S.E., Chen, T., Wu, W., Pruitt, A., Jin, D.S., Jamadagni, P., Carlson, M., Lacadie, C.M., Enriquez, K.D., Li, N., Zhao, D., Ijaz, S., Sakai, C., Szi, C., Rooney, B., Ghosh, M., Nwabudike, I., Gorodezky, A., Chowdhury, S., Zaheer, M., McLaughlin, S., Fernandez, J.M., Wu, J., Eilbott, J.A., Vander Wyk, B., Rihel, J., Papademetris, X., Wang, Z., Hoffman, E.J. (2023) High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways. Cell Reports. 42:112243112243.
Abstract
Advancing from gene discovery in autism spectrum disorders (ASDs) to the identification of biologically relevant mechanisms remains a central challenge. Here, we perform parallel in vivo functional analysis of 10 ASD genes at the behavioral, structural, and circuit levels in zebrafish mutants, revealing both unique and overlapping effects of gene loss of function. Whole-brain mapping identifies the forebrain and cerebellum as the most significant contributors to brain size differences, while regions involved in sensory-motor control, particularly dopaminergic regions, are associated with altered baseline brain activity. Finally, we show a global increase in microglia resulting from ASD gene loss of function in select mutants, implicating neuroimmune dysfunction as a key pathway relevant to ASD biology.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping