Weinschutz Mendes, Hellen;
Neelakantan, Uma;
Liu, Yunqing;
Fitzpatrick, Sarah E;
Chen, Tianying;
Wu, Weimiao;
Pruitt, April;
... Hoffman, Ellen J; + view all
(2023)
High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways.
Cell Reports
, 42
(3)
, Article 112243. 10.1016/j.celrep.2023.112243.
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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.
| Type: | Article |
|---|---|
| Title: | High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2023.112243 |
| Publisher version: | https://doi.org/10.1111/10.1016/j.celrep.2023.1122... |
| Language: | English |
| Additional information: | © 2023 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | autism spectrum disorder, genetics, zebrafish, neurodevelopment, dopaminergic neurons, microglia |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10167044 |
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