Transcriptional Control of Parallel-Acting Pathways That Remove Specific Presynaptic Proteins in Remodeling Neurons

Area of Science:

• Neuroscience
• Molecular Biology
• Developmental Biology

Background:

• Synaptic pruning is crucial for neural circuit refinement during development.
• Mechanisms regulating synaptic disassembly, particularly presynaptic apparatus removal, remain largely uncharacterized.
• Previous work identified the epithelial sodium channel ENaC/UNC-8 in activity-dependent presynaptic protein removal.

Purpose of the Study:

• To elucidate the developmental pathways governing synaptic disassembly.
• To identify regulatory mechanisms controlling the removal of presynaptic components during neural circuit development.
• To investigate the role of the conserved transcription factor Iroquois/IRX-1 in synaptic elimination.

Main Methods:

• Utilized *Caenorhabditis elegans* as a model organism.
• Investigated the regulation of synaptic protein removal in remodeling GABAergic neurons.
• Examined the role of the transcription factor Iroquois/IRX-1 and the epithelial sodium channel UNC-8 in synaptic disassembly.

Main Results:

• The transcription factor Iroquois/IRX-1 regulates both UNC-8 expression and an independent, parallel pathway for presynaptic terminal dismantling.
• The IRX-1-regulated, UNC-8-independent pathway specifically targets Munc13/UNC-13 and ELKS, proteins essential for synaptic vesicle fusion.
• These findings highlight the critical role of transcriptional regulation in developmental synapse elimination.

Conclusions:

• Synaptic disassembly is orchestrated by parallel-acting pathways that target distinct active zone proteins.
• The IRX-1 transcription factor plays a key role in coordinating synapse elimination through multiple mechanisms.
• Synaptic structure is dismantled in an organized manner, rather than through wholesale destruction.