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Highwire regulates synaptic growth in Drosophila.

H I Wan¹, A DiAntonio, R D Fetter

¹Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.

|June 6, 2000

Summary

The highwire (hiw) gene regulates synaptic growth at the Drosophila neuromuscular junction (NMJ). Mutations in hiw cause excessive synapse growth but reduced physiological function.

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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.

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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.