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The intrinsic ability of injured neurons to degenerate and regenerate their axons facilitates nervous system repair; however, this ability is not engaged in all neurons and injury locations. Here, we investigate the regulation of a conserved axonal injury response pathway with respect to the location of damage in branched motoneuron (MN) axons in Drosophila larvae. The dileucine zipper kinase (DLK; also known as MAP3K12 in mammals and Wallenda (Wnd) in Drosophila) is a key regulator of diverse responses to axonal injury. In three different populations of MNs, we observed the same striking result that Wnd/DLK signaling becomes activated only in response to injuries that remove all synaptic terminals. Injuries that spared even a small part of a synaptic terminal were insufficient to activate Wnd/DLK signaling, despite the presence of extensive axonal degeneration. The regulation of injury-induced Wnd/DLK signaling occurs independently of its previously known regulator, the Hiw/PHR ubiquitin ligase. We propose that Wnd/DLK signaling regulation is linked to the trafficking of a synapse-to-nucleus axonal cargo and that this mechanism enables neurons to respond to impairments in synaptic connectivity.
Pubmed ID: 41159443
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View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal targets Green Fluorescent Protein (GFP)
View all literature mentionsThis polyclonal targets DsRed
View all literature mentionsThis monoclonal targets beta-galactosidase
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mW.hs]=GawB}tey[5053A]/TM6B, Tb[+] from BDSC.
View all literature mentionsDrosophila melanogaster with name P{w[+m*]=GAL4}BG380; In(3L)D, D[1]/TM3, Sb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.GL00282}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{ry[+t7.2]=A92}puc[E69]/TM3, Sb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*] hiw[DeltaN] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS05772}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=Tdc2-GAL4.C}2 from BDSC.
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