%0 Journal Article
%A Tedeschi, Andrea
%A Dupraz, Sebastian
%A Curcio, Michele
%A Laskowski, Claudia J
%A Schaffran, Barbara
%A Flynn, Kevin C
%A Da Silva Santos, Telma
%A Stern, Sina
%A Hilton, Brett J
%A Larson, Molly J E
%A Gurniak, Christine B
%A Witke, Walter
%A Bradke, Frank
%T ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS.
%J Neuron
%V 103
%N 6
%@ 0896-6273
%C New York, NY
%I Elsevier
%M DZNE-2020-07840
%P 1073-1085.e6
%D 2019
%X Injured axons fail to regenerate in the adult CNS, which contrasts with their vigorous growth during embryonic development. We explored the potential of re-initiating axon extension after injury by reactivating the molecular mechanisms that drive morphogenetic transformation of neurons during development. Genetic loss- and gain-of-function experiments followed by time-lapse microscopy, in vivo imaging, and whole-mount analysis show that axon regeneration is fueled by elevated actin turnover. Actin depolymerizing factor (ADF)/cofilin controls actin turnover to sustain axon regeneration after spinal cord injury through its actin-severing activity. This pinpoints ADF/cofilin as a key regulator of axon growth competence, irrespective of developmental stage. These findings reveal the central role of actin dynamics regulation in this process and elucidate a core mechanism underlying axon growth after CNS trauma. Thereby, neurons maintain the capacity to stimulate developmental programs during adult life, expanding their potential for plasticity. Thus, actin turnover is a key process for future regenerative interventions.
%K Actins: metabolism
%K Animals
%K Axons: metabolism
%K Axons: pathology
%K Cofilin 1: genetics
%K Cofilin 1: metabolism
%K Cofilin 2: genetics
%K Cofilin 2: metabolism
%K Destrin: genetics
%K Destrin: metabolism
%K Growth Cones: metabolism
%K Growth Cones: pathology
%K Intravital Microscopy
%K Mice
%K Microscopy, Confocal
%K Nerve Regeneration: genetics
%K Neurons: metabolism
%K Neurons: pathology
%K Rats
%K Spinal Cord Injuries: genetics
%K Spinal Cord Injuries: metabolism
%K Spinal Cord Injuries: pathology
%K Time-Lapse Imaging
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:31400829
%2 pmc:PMC6763392
%R 10.1016/j.neuron.2019.07.007
%U https://pub.dzne.de/record/141516