The homeodomain transcriptional regulator DVE-1 directs a program for synapse elimination during circuit remodeling
Open accessPublished version of a preprint
Abstract
The elimination of synapses during circuit remodeling is critical for brain maturation; however, the molecular mechanisms directing synapse elimination and its timing remain elusive. We show that the transcriptional regulator DVE-1, which shares homology with special AT-rich sequence-binding (SATB) family members previously implicated in human neurodevelopmental disorders, directs the elimination of juvenile synaptic inputs onto remodeling C. elegans GABAergic neurons. Juvenile acetylcholine receptor clusters and apposing presynaptic sites are eliminated during the maturation of wild-type GABAergic neurons but persist into adulthood in dve-1 mutants, producing heightened motor connectivity. DVE-1 localization to GABAergic nuclei is required for synapse elimination, consistent with DVE-1 regulation of transcription. Pathway analysis of putative DVE-1 target genes, proteasome inhibitor, and genetic experiments implicate the ubiquitin-proteasome system in synapse elimination. Together, our findings define a previously unappreciated role for a SATB family member in directing synapse elimination during circuit remodeling, likely through transcriptional regulation of protein degradation processes.
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- Authors
- Alexander, K. D., Ramachandran, S., Biswas, K., Lambert, C. M., Russell, J., Oliver, D. B., Armstrong, W., Rettler, M., Liu, S., Doitsidou, M., Bénard, C., Walker, A. K., & Francis, M. M.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- University of Edinburgh (GB)
- Université du Québec à Montréal (CA)
- Corresponding author
- Francis, Michael M.
- ORCID
- Venue
- Nature Communications
- Published
- 2023-11-18
- Volume
- 14
- Issue
- 1
- Pages
- 7520-7520
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10657367
- OpenAlex
- W4388789393
- Cited by
- 9
- References
- 7
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 2
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (RO1NS064263)
- Howard Hughes Medical Institute (GT11432)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (T32GM135701)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- synaptic pruning, homeodomain transcription factor, GABAergic neurons, acetylcholine receptor clusters, synapse maturation, ubiquitin-proteasome system, protein degradation, Caenorhabditis elegans, neurodevelopmental disorders
- MeSH terms
- Animals, Humans, Receptors, Cholinergic, Synapses, Caenorhabditis elegans, Caenorhabditis elegans Proteins, GABAergic Neurons
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