Journal Article

DZNE-2020-07840

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS.

Tedeschi, A.DZNE* ; Dupraz, S.DZNE* ; Curcio, M.DZNE* ; Laskowski, C. J.DZNE* ; Schaffran, B.DZNE* ; Flynn, K. C.DZNE* ; Da Silva Santos, T.DZNE* ; Stern, S.DZNE* ; Hilton, B. J.DZNE* ; Larson, M. J. E. ; Gurniak, C. B. ; Witke, W. ; Bradke, F. (First author)DZNE*

2019
Elsevier New York, NY

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.neuron.2019.07.007

Abstract: 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.

Keyword(s): Actins: metabolism (MeSH) ; Animals (MeSH) ; Axons: metabolism (MeSH) ; Axons: pathology (MeSH) ; Cofilin 1: genetics (MeSH) ; Cofilin 1: metabolism (MeSH) ; Cofilin 2: genetics (MeSH) ; Cofilin 2: metabolism (MeSH) ; Destrin: genetics (MeSH) ; Destrin: metabolism (MeSH) ; Growth Cones: metabolism (MeSH) ; Growth Cones: pathology (MeSH) ; Intravital Microscopy (MeSH) ; Mice (MeSH) ; Microscopy, Confocal (MeSH) ; Nerve Regeneration: genetics (MeSH) ; Neurons: metabolism (MeSH) ; Neurons: pathology (MeSH) ; Rats (MeSH) ; Spinal Cord Injuries: genetics (MeSH) ; Spinal Cord Injuries: metabolism (MeSH) ; Spinal Cord Injuries: pathology (MeSH) ; Time-Lapse Imaging (MeSH)

---

Contributing Institute(s):

1. Axon Growth and Regeneration (AG Bradke)
2. Dynamics of neuronal circuits (AG Tavosanis)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2019

---

Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

---