TY  - JOUR
AU  - Tedeschi, Andrea
AU  - Dupraz, Sebastian
AU  - Curcio, Michele
AU  - Laskowski, Claudia J
AU  - Schaffran, Barbara
AU  - Flynn, Kevin C
AU  - Da Silva Santos, Telma
AU  - Stern, Sina
AU  - Hilton, Brett J
AU  - Larson, Molly J E
AU  - Gurniak, Christine B
AU  - Witke, Walter
AU  - Bradke, Frank
TI  - ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS.
JO  - Neuron
VL  - 103
IS  - 6
SN  - 0896-6273
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2020-07840
SP  - 1073-1085.e6
PY  - 2019
AB  - 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.
KW  - Actins: metabolism
KW  - Animals
KW  - Axons: metabolism
KW  - Axons: pathology
KW  - Cofilin 1: genetics
KW  - Cofilin 1: metabolism
KW  - Cofilin 2: genetics
KW  - Cofilin 2: metabolism
KW  - Destrin: genetics
KW  - Destrin: metabolism
KW  - Growth Cones: metabolism
KW  - Growth Cones: pathology
KW  - Intravital Microscopy
KW  - Mice
KW  - Microscopy, Confocal
KW  - Nerve Regeneration: genetics
KW  - Neurons: metabolism
KW  - Neurons: pathology
KW  - Rats
KW  - Spinal Cord Injuries: genetics
KW  - Spinal Cord Injuries: metabolism
KW  - Spinal Cord Injuries: pathology
KW  - Time-Lapse Imaging
LB  - PUB:(DE-HGF)16
C6  - pmid:31400829
C2  - pmc:PMC6763392
DO  - DOI:10.1016/j.neuron.2019.07.007
UR  - https://pub.dzne.de/record/141516
ER  -