ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS.

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.

The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS.

Injuries to the adult CNS often result in permanent disabilities because neurons lose the ability to regenerate their axon during development. Here, whole transcriptome sequencing and bioinformatics analysis followed by gain- and loss-of-function experiments identified Cacna2d2, the gene encoding the Alpha2delta2 subunit of voltage-gated calcium channels (VGCCs), as a developmental switch that limits axon growth and regeneration. Cacna2d2 gene deletion or silencing promoted axon growth in vitro.

PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system.

Axonal regenerative failure is a major cause of neurological impairment following central nervous system (CNS) but not peripheral nervous system (PNS) injury. Notably, PNS injury triggers a coordinated regenerative gene expression programme. However, the molecular link between retrograde signalling and the regulation of this gene expression programme that leads to the differential regenerative capacity remains elusive.

In vivo imaging: a dynamic imaging approach to study spinal cord regeneration.

Upon spinal cord injury, severed axons and the surrounding tissue undergo a series of pathological changes, including retraction of proximal axon ends, degeneration of distal axon ends and formation of a dense fibrotic scar that inhibits regenerative axonal growth. Until recently it was technically challenging to study these dynamic events in the mammalian central nervous system. Here, we describe and discuss the recently established genetic tract tracing approach of in vivo imaging.

Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury.

Hypertrophic scarring and poor intrinsic axon growth capacity constitute major obstacles for spinal cord repair. These processes are tightly regulated by microtubule dynamics. Here, moderate microtubule stabilization decreased scar formation after spinal cord injury in rodents through various cellular mechanisms, including dampening of transforming growth factor-β signaling.