GSBS Student Publications

Student Author(s)

Thomas Burdett

GSBS Program

Neuroscience

UMMS Affiliation

Department of Neurobiology; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program

Date

7-8-2014

Document Type

Article

Medical Subject Headings

Alleles; Animals; *Axons; Drosophila; Genes, Dominant; Genes, Insect; Genes, Recessive; Mosaicism; Wings, Animal

Disciplines

Genetics | Molecular and Cellular Neuroscience

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 ( approximately 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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9965-70. doi: 10.1073/pnas.1406230111. Epub 2014 Jun 23. Link to article on publisher's site

DOI of Published Version

10.1073/pnas.1406230111

Comments

Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.

Related Resources

Link to Article in PubMed

Keywords

glial response, neurodegeneration

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

24958874

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.