In Drosophila’s Giant Fiber System, loss or mutation of Frazzled weakens gap junctions, delays neural responses, and reduces muscle control due to impaired electrical coupling.

Frazzled, a DCC-like protein in mammals, serves a dual role in neural development by guiding neurons to targets and controlling synapse formation.

Researchers plan to investigate whether these mechanisms operate in mammals and other organisms and how Frazzled-related pathways affect broader CNS processes.

Collaborators include Juan Lopez (first author) and Rodney Murphey (senior author) from FAU, with a team across FAU’s imaging and biology departments.

Frazzled’s intracellular portion rescues both the wiring of synapses and the speed of neural communication, signaling that Frazzled’s regulation of gene activity is essential for forming functional gap junctions.

The project features contributions from Juan Lopez and Rodney Murphey as core FAU investigators, with co-authors spanning imaging and biology groups.

Lead investigator Murphey emphasizes a combined experimental and computational approach to reveal how Frazzled shapes neural connections, with future work exploring mammalian relevance and implications for learning, memory, and neural repair.

Findings point to a conserved, broader role for Frazzled-like pathways across species in shaping neural networks and potentially informing neural development, learning, memory, and injury repair.

Evidence suggests conservation of these mechanisms across species, with potential relevance to mammalian neural circuits and cognitive functions.

The study highlights cross-species conservation and implications for learning, memory, and recovery after neural injury.

The research integrated genetics, imaging, physiology, and computational modeling to dissect how Frazzled shapes both physical wiring and functional connectivity.

The work appears in eNeuro, volume 12, issue 10, 2025, under a title addressing Frazzled and neural wiring in Drosophila.

A computational model of the Giant Fiber system shows that even small changes in gap junction density can strongly affect firing reliability and speed, aligning with experimental results.

Combining experiments and modeling demonstrates that alterations in gap junction density materially impact the speed and precision of neural signaling.

Overall, the integrated approach supports that gap junction density is a key determinant of neural signaling dynamics in the Giant Fiber system.