ArticleProceedings of the National Academy of Sciences of the United States of America2014
Rapid in vivo forward genetic approach for identifying axon death genes in Drosophila.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 81 citations in OpenAlex.
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- Sleep rescues age-associated loss of glial engulfment.PLoS genetics · 2026Article
- Cholinergic and Glutamatergic Axons Differentially Require Glial Support in the Drosophila PNS.Glia · 2025Article
- Study of Axonal Injury and Degeneration inCold Spring Harbor protocols · 2025Article
- Wallerian Degeneration and Clearance of Olfactory Receptor Neuron Axons followingCold Spring Harbor protocols · 2025Article
- Molecular profiling of invertebrate glia.Glia · 2025Review
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- Cdk12 maintains the integrity of adult axons by suppressing actin remodeling.Cell death discovery · 2023Article
- COPI-regulated mitochondria-ER contact site formation maintains axonal integrity.Cell reports · 2023Article
- LC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models.Nature communications · 2023Article
- A toolkit for converting Gal4 into LexA and Flippase transgenes in Drosophila.G3 (Bethesda, Md.) · 2023Article
- Glial TGFβ activity promotes neuron survival in peripheral nerves.The Journal of cell biology · 2023Article
- Review
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- Tau-mediated axonal degeneration is prevented by activation of the WldBrain communications · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Axons damaged by acute injury, toxic insults, or neurodegenerative diseases execute a poorly defined autodestruction signaling pathway leading to widespread fragmentation and functional loss. Here, we describe an approach to study Wallerian degeneration in the Drosophila L1 wing vein that allows for analysis of axon degenerative phenotypes with single-axon resolution in vivo. This method allows for the axotomy of specific subsets of axons followed by examination of progressive axonal degeneration and debris clearance alongside uninjured control axons. We developed new Flippase (FLP) reagents using proneural gene promoters to drive FLP expression very early in neural lineages. These tools allow for the production of mosaic clone populations with high efficiency in sensory neurons in the wing. We describe a collection of lines optimized for forward genetic mosaic screens using MARCM (mosaic analysis with a repressible cell marker; i.e., GFP-labeled, homozygous mutant) on all major autosomal arms (∼95% of the fly genome). Finally, as a proof of principle we screened the X chromosome and identified a collection eight recessive and two dominant alleles of highwire, a ubiquitin E3 ligase required for axon degeneration. Similar unbiased forward genetic screens should help rapidly delineate axon death genes, thereby providing novel potential drug targets for therapeutic intervention to prevent axonal and synaptic loss.
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