An activity-regulated transcriptional program directly drives synaptogenesis.

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Synaptic molecular composition and architecture are well-studied.
• Genetic programs controlling synaptic gene expression and modulation remain less understood.

Purpose of the Study:

• To identify genetic programs that activate synaptic gene expression.
• To understand the modulation of these programs in activity-dependent synaptogenesis.

Main Methods:

• Utilized Caenorhabditis elegans dopaminergic neurons.
• Investigated the roles of EGL-43/MECOM and FOS-1/FOS transcription factors.
• Performed promoter binding assays and gene expression analysis.

Main Results:

• EGL-43 and FOS-1 control an activity-dependent synaptogenesis program.
• Loss of EGL-43 or FOS-1 significantly reduces presynaptic protein expression.
• Both factors directly bind to synaptic gene promoters and co-activate transcription with CUT homeobox factors.
• egl-43 and fos-1 mutually regulate each other's expression.
• Enhanced FOS-1 binding to the egl-43 locus increases presynaptic protein and synaptic function.
• EGL-43 regulates various transcription factors, including activity-regulated and developmental factors, defining dopaminergic identity.

Conclusions:

• A robust genetic program involving EGL-43 and FOS-1 underlies activity-regulated synapse formation during development.
• This program is essential for establishing and maintaining presynaptic protein expression and synaptic function.