Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons.
Overview
- Department of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
- MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
- Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany
- Medical Proteome Analysis, Center for Protein Diagnostics (PRODI), Ruhr-University Bochum, 44801 Bochum, Germany
- Department of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK
- Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
Abstract
ZNF804A was among the first genes robustly associated with schizophrenia based on findings from large-scale genomic studies. Previous research has implicated ZNF804A in the regulation of gene expression and synaptic function, but the role of this gene in neurodevelopment and in schizophrenia pathogenesis remains unclear. To study its function during neurodevelopment, we generated isogenic human induced pluripotent stem cells with reduced ZNF804A expression, differentiated them into developing cortical glutamatergic neurons, and studied their transcriptomic, synaptic, and protein signatures. Mutant neurons showed modest evidence for changes in gene expression. However, high-content confocal imaging revealed increased excitatory synapse density in mutant neurons. Cell compartment–specific proteomic analysis further revealed that mutant neurons had higher levels of ribosomal and translational proteins within neurites, and high-content imaging confirmed increased local protein synthesis efficiency. Overall, these results demonstrate that in human developing cortical glutamatergic neurons, ZNF804A regulates excitatory synapse formation potential via increased local protein translation.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE254523, at NCBI GEO; found in “Data, code, and materials availability:”
Other data links
- ncbi.nlm.nih.gov/
geo , NCBI; found in “Data, code, and materials availability:”
Data, code, and materials availability
All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 17 authors, 12 MeSH terms, 7 funders, 84 references.
Cite
This paper
Sichlinger, L., Hausherr, M., Guerrisi, S., Dutan-Polit, L., Chennell, G., Nagy, R., Matuleviciute, R., Nasser, F., Farkas, S., Bamford, R. A., Leung, S. K., Duarte, R. R. R., Powell, T. R., Mill, J., Marcus, K., Vernon, A. C., & Srivastava, D. P. (2026). Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons. Science advances, 12(21), eaea0755. https://
BibTeX
@article{sichlinger2026s
author = {Sichlinger, Laura and Hausherr, Maximilian and Guerrisi, Sara and Dutan-Polit, Lucia and Chennell, George and Nagy, Roland and Matuleviciute, Rugile and Nasser, Fatema and Farkas, Szidonia and Bamford, Rosemary A and Leung, Szi Kay and Duarte, Rodrigo R R and Powell, Timothy R and Mill, Jonathan and Marcus, Katrin and Vernon, Anthony C and Srivastava, Deepak P},
title = {{Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons}},
journal = {Science advances},
year = {2026},
month = may,
volume = {12},
number = {21},
pages = {eaea0755},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/
url = {https://
pmid = {42160410},
pmcid = {PMC13189102}
}
RIS
TY - JOUR
AU - Sichlinger, Laura
AU - Hausherr, Maximilian
AU - Guerrisi, Sara
AU - Dutan-Polit, Lucia
AU - Chennell, George
AU - Nagy, Roland
AU - Matuleviciute, Rugile
AU - Nasser, Fatema
AU - Farkas, Szidonia
AU - Bamford, Rosemary A
AU - Leung, Szi Kay
AU - Duarte, Rodrigo R R
AU - Powell, Timothy R
AU - Mill, Jonathan
AU - Marcus, Katrin
AU - Vernon, Anthony C
AU - Srivastava, Deepak P
TI - Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/
VL - 12
IS - 21
SP - eaea0755
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/
UR - https://
LA - en
ER -
CSL-JSON
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