Year: 2024
Type: article
Abstract: 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.
Source: Nature Neuroscience
Institutions: Howard Hughes Medical Institute, Stanford University, Max Planck Florida Institute for Neuroscience, Stony Brook University, The University of Texas Southwestern Medical Center, VA Northern California Health Care System, University of California, Davis, University of North Carolina at Chapel Hill, University of Michigan
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,290
Funders: Howard Hughes Medical Institute, U.S. Department of Health and Human Services, 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
Awards: Mechanisms of synaptic specificity in C. elegans, G152341094, G1641065565, G1994913649, RegulomeDB: A Resource for the Human Regulome, G2539368543, Transcriptional regulation of morphogenetic behavior and invasive cell fate specification in C. elegans, G3789166473, G4101087687, G5043028391, Mechanisms of Presynaptic Maintenance in C. elegans, High Throughput DNA Sequencer Upgrade, G6111888376, Elucidating the mechanisms underlying cell cycle regulation of invasive behavior, G7193899933, G9000028377, Caenorhabditis Genetics Center, Predicting the Impact of Genomic Variation on Cellular States
OpenAlex ID: W4401339274