Year-end Sale % OFF 
Abstract
The mechanisms underlying axon regeneration in mature neurons are relevant to the understanding of normal nervous system maintenance and for developing therapeutic strategies for injury. Here, we report novel pathways in axon regeneration, identified by extending our previous function-based screen using the C. elegans mechanosensory neuron axotomy model. We identify an unexpected role of the nicotinamide adenine dinucleotide (NAD+) synthesizing enzyme, NMAT-2/NMNAT, in axon regeneration. NMAT-2 inhibits axon regrowth via cell-autonomous and non-autonomous mechanisms. NMAT-2 enzymatic activity is required to repress regrowth. Further, we find differential requirements for proteins in membrane contact site, components and regulators of the extracellular matrix, membrane trafficking, microtubule and actin cytoskeleton, the conserved Kelch-domain protein IVNS-1, and the orphan transporter MFSD-6 in axon regrowth. Identification of these new pathways expands our understanding of the molecular basis of axonal injury response and regeneration.
Highlights
Axon regeneration after injury is an important and conserved biological process in many animals, involving a large number of genes and pathways (He and Jin, 2016; Mahar and Cavalli, 2018; Tedeschi and Bradke, 2017)
The combined analyses of >1200 genes reinforce the conclusion that regenerative axon regrowth requires many genetic pathways, most of which are not involved in developmental axon outgrowth or guidance
Functional screening for axon regeneration phenotypes is a powerful approach to identify novel regulators of axon regrowth after injury
Summary
Axon regeneration after injury is an important and conserved biological process in many animals, involving a large number of genes and pathways (He and Jin, 2016; Mahar and Cavalli, 2018; Tedeschi and Bradke, 2017). Axon regeneration after injury requires rapid sealing of the damaged plasma membrane (PM) and subsequent formation of growth cones, leading to regrowth and extension from damaged proximal axons These cellular changes involve numerous molecular pathways, starting with rapid calcium influx at injury sites (GhoshRoy et al, 2010; Rishal and Fainzilber, 2014; Wolf et al, 2001), retrograde injury signaling, transcriptional reprogramming to re-structuring of the cytoskeleton and re-organization of the extracellular matrix (ECM) (Blanquie and Bradke, 2018). Our studies of genes encoding lipid or phospholipid metabolic enzymes indicate extensive functional redundancy This expanded screen reinforces several themes from the previous study, such as the inhibitory role of ECM components and the permissive role of MT stabilization (Chen et al, 2011). Our findings highlight the molecular complexity of axon regeneration and provide the genetic framework for a more comprehensive understanding of axon regeneration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
