title: A conditioning lesion protects axons from degeneration via the Wallenda/DLK MAP kinase signaling cascade.
abstract: Axons are vulnerable components of neuronal circuitry, and neurons are equipped with mechanisms for responding to axonal injury. A highly studied example of this is the conditioning lesion, in which neurons that have been previously injured have an increased ability to initiate new axonal growth (Hoffman, 2010). Here we investigate the effect of a conditioning lesion on axonal degeneration, which occurs in the distal stump after injury, and also occurs in neuropathies and neurodegenerative disorders (Coleman, 2005). We found that Drosophila motoneuron axons that had been previously injured had an increased resiliency to degeneration. This requires the function of a conserved axonal kinase, Wallenda (Wnd)/DLK, and a downstream transcription factor. Because axonal injury leads to acute activation of Wnd (Xiong et al., 2010), and overexpression studies indicate that increased Wnd function is sufficient to promote protection from degeneration, we propose that Wnd regulates an adaptive response to injury that allows neurons to cope with axonal stress.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Xiong
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Collins
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001369:Axons / Q000201:enzymology* / Q000473:pathology; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D009046:Motor Neurons / Q000201:enzymology* / Q000473:pathology; D009409:Nerve Crush / Q000379:methods; D009469:Neuromuscular Junction / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D013312:Stress, Physiological / Q000502:physiology; D014855:Wallerian Degeneration / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D029721:Drosophila Proteins; D020930:MAP Kinase Kinase Kinases; C512899:wnd protein, Drosophila