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Citation
Fang, Y., Soares, L., Teng, X., Geary, M., Bonini, N.M. (2012). A novel Drosophila model of nerve injury reveals an essential role of nmnat in maintaining axonal integrity.  Curr. Biol. 22(7): 590--595.
FlyBase ID
FBrf0218051
Publication Type
Research paper
Abstract

Axons damaged by acute injury, toxic insults, or during neurodegenerative diseases undergo Wallerian or Wallerian-like degeneration, which is an active and orderly cellular process, but the underlying mechanisms are poorly understood. Drosophila has been proven to be a successful system for modeling human neurodegenerative diseases. In this study, we established a novel in vivo model of axon injury using the adult fly wing. The wing nerve highlighted by fluorescent protein markers can be directly visualized in living animals and be precisely severed by a simple wing cut, making it highly suitable for large-scale screening. Using this model, we confirmed an axonal protective function of Wld(S) and nicotinamide mononucleotide adenylyltransferase (Nmnat). We further revealed that knockdown of endogenous Nmnat triggered spontaneous, dying-back axon degeneration in vivo. Intriguingly, axonal mitochondria were rapidly depleted upon axotomy or downregulation of Nmnat. The injury-induced mitochondrial loss was dramatically suppressed by upregulation of Nmnat, which also protected severed axons from degeneration. However, when mitochondria were genetically eliminated from axons, upregulation of Nmnat was no longer effective to suppress axon degeneration. Together, these findings demonstrate an essential role of endogenous Nmnat in maintaining axonal integrity that may rely on and function by stabilizing mitochondria.

Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC3347919 (PMC) (EuropePMC)
Related Publication(s)
Note

Axon degeneration: where the Wlds things are.
Wang and Barres, 2012, Curr. Biol. 22(7): R221--R223 [FBrf0219143]

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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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Curr. Biol.
    Title
    Current Biology
    Publication Year
    1991-
    ISBN/ISSN
    0960-9822
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    Alleles (9)
    Genes (10)
    Natural transposons (1)
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    Experimental Tools (1)
    Transgenic Constructs (8)
    Transcripts (1)