Repulsive Wnt Signaling Inhibits Axon Regeneration after CNS Injury

Axons in the adult central nervous system (CNS) fail to regenerate after injury due to inhibitory molecules and a lack of growth-stimulating molecules. This study investigates whether axon guidance molecules, specifically Wnts, regulate regenerative growth after spinal cord injury in adults. Wnts are a family of signaling proteins that guide axons during development. The researchers found that certain Wnt genes (Wnt1, Wnt4, and Wnt5a) are reinduced after spinal cord injury, despite being normally undetectable in adult spinal cord. Blocking the repulsive Wnt receptor Ryk with antibodies either prevented the retraction of corticospinal tract (CST) axons or promoted their regrowth after injury. Furthermore, it enhanced the sprouting of CST collateral branches around the injury site, suggesting that repulsive Wnt signaling inhibits axon regeneration.

• 1
  The study found that Wnt1 and Wnt5a, known repellents of corticospinal tract (CST) axons, were rapidly and broadly induced in the spinal cord gray matter after unilateral hemisection.
• 2
  The repulsive Wnt receptor Ryk was also induced in the lesion area and found on the lesioned CST axons, indicating its potential role in inhibiting axon regeneration.
• 3
  Injection of function-blocking Ryk antibodies prevented the retraction of CST axons, promoted their regrowth, and enhanced the sprouting of CST collateral branches around the injury site.