An activity-regulated transcriptional program directly drives synaptogenesis
Although the molecular composition and architecture of synapses have been widely explored, much less is known about what genetic programs directly activate synaptic gene expression and how they are modulated. Here, using Caenorhabditis elegans dopaminergic neurons, we reveal that EGL-43/MECOM and FOS-1/FOS control an activity-dependent synaptogenesis program. Loss of either factor severely reduces presynaptic protein expression. Both factors bind directly to promoters of synaptic genes and act together with CUT homeobox transcription factors to activate transcription. egl-43 and fos-1 mutually promote each other's expression, and increasing the binding affinity of FOS-1 to the egl-43 locus results in increased presynaptic protein expression and synaptic function. EGL-43 regulates the expression of multiple transcription factors, including activity-regulated factors and developmental factors that define multiple aspects of dopaminergic identity. Together, we describe a robust genetic program underlying activity-regulated synapse formation during development.
Authors
- Bing Xu (ORCID: https://orcid.org/0000-0001-9159-2512)
- David Q. Matus (ORCID: https://orcid.org/0000-0002-1570-5025)
- Wendy A. Herbst (ORCID: https://orcid.org/0000-0002-8364-907X)
- Alan P. Boyle (ORCID: https://orcid.org/0000-0002-2081-1105)
- Taylor N. Medwig-Kinney (ORCID: https://orcid.org/0000-0001-7989-3291)
- Hongwen Chen (ORCID: https://orcid.org/0000-0002-1065-9808)
- Anay R. Reddy
- Kang Shen (ORCID: https://orcid.org/0000-0003-4059-8249)
- Yutong Xiao (ORCID: https://orcid.org/0000-0001-7279-3423)
- Yang K. Xiang (ORCID: https://orcid.org/0000-0003-1786-9143)
- Callista Yee (ORCID: https://orcid.org/0000-0002-2928-492X)
- Wan Zhang (ORCID: https://orcid.org/0000-0003-1896-8186)
Institutions
- University of North Carolina at Chapel Hill (US)
- Howard Hughes Medical Institute (US)
- Neurosciences Institute (US)
- University of Michigan (US)
- Max Planck Florida Institute for Neuroscience (US)
- VA Northern California Health Care System (US)
- Stony Brook University (US)
- University of California, Davis (US)
- The University of Texas Southwestern Medical Center (US)
- Stanford University (US)
Publication Details
- Journal
- Nature Neuroscience
- Published
- 2024-08-05
- DOI
- https://doi.org/10.1038/s41593-024-01728-x
- Citations
- 12
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- Howard Hughes Medical Institute
- University of Minnesota
- Parker Institute for Cancer Immunotherapy
- Human Frontier Science Program
- National Institutes of Health
- Stanford Research Computing Center, Stanford University
- National Human Genome Research Institute
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Office of Research Infrastructure Programs, National Institutes of Health