Genome-wide analysis reveals pathways important for the development and maturation of excitatory synaptic connections to GABAergic neurons
Open accessPreprint — published as 10.1093/g3journal/jkag028
Abstract
A high degree of cell and circuit-specific regulation has presented challenges for efforts to precisely define molecular mechanisms controlling synapse formation and maturation. Here, we pursue an unbiased forward genetic approach to identify C. elegans genes involved in the formation and maturation of cholinergic synaptic connections with GABAergic motor neurons as indicated by the distribution of GFP-tagged postsynaptic acetylcholine receptors (AChR) on GABAergic dendrites. We identified mutations in 3 genes that identify key processes in synapse/circuit maturation. Mutation of the RUN domain ( R PIP8, U NC-14, and N ESCA) cargo adaptor gene unc-14 dramatically impacts overall GABAergic neuron morphology and dendritic spines. Mutation of the nicotinic acetylcholine alpha subunit gene unc-63 causes a failure in AChR assembly in GABAergic neurons but does not significantly alter dendritic spine structure or abundance. Finally, a mutation in the Liprin-α synaptic scaffold gene syd-2 severely disrupts both dendritic spines and AChR localization. The identification of these three genes from our screen highlights how mechanisms for cargo trafficking, receptor assembly, and synapse structural organization each make distinct contributions to synapse assembly and circuit connectivity.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In invertebrate models, the Liprin-alpha (syd-2) scaffold is crucial for coordinating cargo trafficking and the structural organization of dendritic spines.
“In invertebrate models, the Liprin-alpha (syd-2) scaffold is crucial for coordinating cargo trafficking and the structural organization of dendritic spines [77].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [77]
The section “Mutation of syd-2/Liprin α disrupts dendritic spine formation” reports that syd-2 mutants have fewer dendritic spines and says SYD-2 was previously implicated in cargo trafficking. It does not establish that SYD-2 coordinates cargo trafficking with dendritic-spine organization; the authors describe how SYD-2 affects spines as unresolved. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cited by
Sorted by citations
Molecular Physiology of the Neuronal Synapse
Ramírez-Expósito, M. J., Cueto-Ureña, C., & Martínez-Martos, J. M. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48010088 · Cited by 6 · see citing works
- Authors
- Oliver, D. B., Ramachandran, S., Biswas, K., Bénard, C. Y., Doitsidou, M., McKillop, H., Genao, N., Lemons, M. L., & Francis, M. M.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Université du Québec à Montréal (CA)
- University of Edinburgh (GB)
- Corresponding author
- Francis, Michael M.
- ORCID
- Venue
- G3 Genes Genomes Genetics
- Publisher
- openRxiv
- Published
- 2025-07-06
- Volume
- 16
- Issue
- 4
- ISSN
- 2160-1836 (ISSN-L)
- PMC
- PMC12236491
- OpenAlex
- W7128361751
- Cited by
- 1
- References
- 0
- Citations by year
- 2026: 1
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- G3 Genes Genomes Genetics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed Central (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (RO1NS064263)
- National Science Foundation (IOS1755019, IOS1754986)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- synaptogenesis, synapse maturation, GABAergic motor neurons, nicotinic acetylcholine receptors, dendritic spines, Liprin-α, cargo trafficking, synaptic scaffolds, Caenorhabditis elegans, forward genetic screen, dendritic spine morphology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
