Highwire regulates synaptic growth in Drosophila.

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Synaptic connections, particularly the glutamatergic neuromuscular junction (NMJ) in Drosophila, undergo dynamic growth and regulation during larval development.
• The highwire (hiw) gene was identified through behavioral and anatomical screens for its role in modulating synaptic structure.

Purpose of the Study:

• To investigate the function of the highwire (hiw) gene in regulating synaptic growth and structure at the Drosophila NMJ.
• To characterize the physiological and ultrastructural consequences of hiw mutations on NMJ synapses.

Main Methods:

• Utilized a forward genetic screen in Drosophila melanogaster, including behavioral and anatomical analyses.
• Examined NMJ morphology, ultrastructure, and physiological function in wild-type and hiw mutant larvae.

Main Results:

• hiw mutants exhibit normal motor axon pathfinding and initial synapse formation.
• NMJ synapses in hiw mutants display exuberant growth, characterized by increased bouton number and expanded branching.
• Ultrastructural analysis revealed normal synapse morphology, but physiological recordings showed reduced quantal content.
• The highwire protein is localized to the periactive zone of presynaptic terminals, a region also occupied by Fasciclin II, another regulator of synaptic growth.

Conclusions:

• The highwire (hiw) gene is a critical regulator of synaptic growth at the Drosophila NMJ.
• While hiw promotes synapse expansion, its absence leads to altered synaptic physiology, specifically reduced quantal content.
• HIW's localization suggests a role in coordinating synaptic growth with functional output.