ArticleGenetics2025
Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories.
Article in Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- The contactin rig-6 transiently promotes GABA neuron remodeling with a sustained impact on male mating behavior in C. elegans.Genetics · 2026Article
- Insertion of rare autism variants in synaptic genes induce novel behavioral phenotypes inbioRxiv : the preprint server for biology · 2025Article
- Research progress inFrontiers in neurologyReview
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8 authors.
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Abstract
Variation in over 100 genes is now associated with increased risk for autism and related neurodevelopmental conditions, but how this variation results in distinct and overlapping behavioral changes is still not well understood. Recent efforts have focused on screening many autism genes at once for functional and phenotypic convergence, and identified subsets that are crucial for many early steps of neurodevelopment. Few studies have screened later steps of neurodevelopment, circuit function, circuit plasticity, or behaviors. We screened 20 conserved autism-associated genes for impact on experience-dependent neuron remodeling in Caenorhabditis elegans. Loss of unc-44/ANK2, set-4/KMT5B, daf-18/PTEN, gap-2/SYNGAP1, and chd-1/CHD2/8 increased, while unc-36/CACNA2D3 decreased, neurite outgrowth of the GABAergic DVB neuron in adults. Although daf-18/PTEN, set-4/KMT5B, and unc-44/ANK2 had convergent phenotypes, they arise from distinct temporal trajectories with differential impact on DVB presynaptic morphology. Screening for the DVB regulated spicule protraction behavior identified multiple autism genes involved, but only unc-44/ANK2 and unc-36/CACNA2D3 were shared between screens. Application of a metric geometry computational framework (CAJAL) to the DVB morphology dataset identified 5 additional genes that impact DVB morphology, including unc-2/CACNA1A and unc-10/RIMS1, which also significantly impacted behavior. This work defines new regulators and molecular mechanisms of experience-dependent neuron remodeling and circuit plasticity, and further links these processes with conserved autism genes. It also demonstrates the utility of using intact, behavior generating circuits in C. elegans, to screen for novel roles for conserved autism genes.
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