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Neukomm, L.J., Burdett, T.C., Gonzalez, M.A., Züchner, S., Freeman, M.R. (2014). Rapid in vivo forward genetic approach for identifying axon death genes in Drosophila.  Proc. Natl. Acad. Sci. U.S.A. 111(27): 9965--9970.
FlyBase ID
FBrf0225607
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC4103363 (PMC) (EuropePMC)
Related Publication(s)
Note

Hope on the (fruit) fly: the Drosophila wing paradigm of axon injury.
Fang and Bonini, 2015, Neural Regen. Res. 10(2): 173--175 [FBrf0228107]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference