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High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways.
Weinschutz Mendes, Hellen; Neelakantan, Uma; Liu, Yunqing; Fitzpatrick, Sarah E; Chen, Tianying; Wu, Weimiao; Pruitt, April; Jin, David S; Jamadagni, Priyanka; Carlson, Marina; Lacadie, Cheryl M; Enriquez, Kristen D; Li, Ningshan; Zhao, Dejian; Ijaz, Sundas; Sakai, Catalina; Szi, Christina; Rooney, Brendan; Ghosh, Marcus; Nwabudike, Ijeoma; Gorodezky, Andrea; Chowdhury, Sumedha; Zaheer, Meeraal; McLaughlin, Sarah; Fernandez, Joseph M; Wu, Jia; Eilbott, Jeffrey A; Vander Wyk, Brent; Rihel, Jason; Papademetris, Xenophon; Wang, Zuoheng; Hoffman, Ellen J.
Affiliation
  • Weinschutz Mendes H; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Neelakantan U; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Liu Y; Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA.
  • Fitzpatrick SE; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA; MD-PhD Program, Yale School of Medicine, New Haven, CT 06510, USA.
  • Chen T; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Wu W; Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA.
  • Pruitt A; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA.
  • Jin DS; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA; Department of Neurology, Yale School of Medicine, New Haven, CT 065
  • Jamadagni P; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Carlson M; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA.
  • Lacadie CM; Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06510, USA.
  • Enriquez KD; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Li N; Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA; SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
  • Zhao D; Department of Genetics, Yale Center for Genome Analysis, Yale School of Medicine, New Haven, CT 06510, USA.
  • Ijaz S; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Sakai C; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Szi C; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Rooney B; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Ghosh M; Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
  • Nwabudike I; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA; MD-PhD Program, Yale School of Medicine, New Haven, CT 06510, USA; Department of Psychiatry, Yale School of Medicine, New Haven, CT 06510, USA.
  • Gorodezky A; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Chowdhury S; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Zaheer M; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • McLaughlin S; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Fernandez JM; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Wu J; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Eilbott JA; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Vander Wyk B; Department of Internal Medicine, Section of Geriatrics, Yale School of Medicine, New Haven, CT 06510, USA.
  • Rihel J; Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
  • Papademetris X; Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06510, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06510, USA.
  • Wang Z; Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA.
  • Hoffman EJ; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: ellen.hoffman@yale.edu.
Cell Rep ; 42(3): 112243, 2023 03 28.
Article in En | MEDLINE | ID: mdl-36933215
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autistic Disorder / Autism Spectrum Disorder Limits: Animals Language: En Journal: Cell Rep Year: 2023 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autistic Disorder / Autism Spectrum Disorder Limits: Animals Language: En Journal: Cell Rep Year: 2023 Document type: Article Affiliation country: United States