title: Axon Termination, Pruning, and Synaptogenesis in the Giant Fiber System ofDrosophila melanogasterIs Promoted by Highwire.
abstract: The ubiquitin ligase Highwire has a conserved role in synapse formation. Here, we show that Highwire coordinates several facets of central synapse formation in theDrosophila melanogastergiant fiber system, including axon termination, axon pruning, and synaptic function. Despite the similarities to the fly neuromuscular junction, the role of Highwire and the underlying signaling pathways are distinct in the fly's giant fiber system. During development, branching of the giant fiber presynaptic terminal occurs and, normally, the transient branches are pruned away. However, inhighwiremutants these ectopic branches persist, indicating that Highwire promotes axon pruning.highwiremutants also exhibit defects in synaptic function. Highwire promotes axon pruning and synaptic function cell-autonomously by attenuating a mitogen-activated protein kinase pathway including Wallenda, c-Jun N-terminal kinase/Basket, and the transcription factor Jun. We also show a novel role for Highwire in non-cell autonomous promotion of synaptic function from the midline glia. Highwire also regulates axon termination in the giant fibers, ashighwiremutant axons exhibit severe overgrowth beyond the pruning defect. This excessive axon growth is increased by manipulating Fos expression in the cells surrounding the giant fiber terminal, suggesting that Fos regulates atrans-synaptic signal that promotes giant fiber axon growth.
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida 33431.
authors.forename: Melissa
authors.initials: M
authors.lastname: Borgen
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida 33431.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Rowland
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida 33431.
authors.forename: Jana
authors.initials: J
authors.lastname: Boerner
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida 33431.
authors.forename: Brandon
authors.initials: B
authors.lastname: Lloyd
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida 33431.
authors.forename: Aruna
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida 33431 rmurphey@fau.edu.
authors.forename: Rodney
authors.initials: R
authors.lastname: Murphey
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000071446:Neuronal Outgrowth / Q000235:genetics*; D013569:Synapses / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; C409633:HIW protein, Drosophila; D009419:Nerve Tissue Proteins
keywords: Fos; giant fiber; highwire; pruning; synaptogenesis