A growing field: the regulation of axonal regeneration by Wnt signaling

Neural Regen Res, 2018 · DOI: 10.4103/1673-5374.224359 · Published: January 1, 2018

Regenerative Medicine Neurology Genetics

Simple Explanation

Wnt signaling pathways are crucial for cell growth, specialization, and movement during development. These pathways are categorized into canonical (Wnt/β-catenin) and non-canonical types. In the central nervous system, Wnt ligands influence how axons extend, navigate, and form connections. Recent research suggests Wnt signaling can also help regenerate damaged axons in the optic nerve and spinal cord. A key challenge in neuroscience is finding ways to stimulate axon regeneration after injuries. Studies show that Wnt signaling can promote both nerve cell survival and axon growth, offering potential therapeutic strategies.

Study Duration

Not specified

Participants

Mammalian and fish model systems

Evidence Level

Review

Key Findings

1
Activation of Wnt/β-catenin signaling in retinal neurons and radial glia promotes neuronal survival and axonal growth.
2
Wnt signaling in fibroblast-like cells induces collagen XII expression and deposition at the lesion site, facilitating axonal growth.
3
Wnt3a promotes neurite outgrowth, increases neuronal function, and induces repair after spinal cord contusion injury in adult rats.

Research Summary

This review summarizes experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discusses possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement.

Practical Implications

Therapeutic Potential

Wnt signaling has therapeutic potential for axonal regeneration after injury, warranting further study to define its mechanism of action and maximize regeneration efficacy.

Cell-Specific Targeting

Understanding the cell-specific effects of Wnt signaling is crucial. Activating Wnt in certain cells (e.g., neurons, radial glia) promotes regeneration, while activating it in others (e.g., reactive glia) can hinder it.

Combination Therapies

Wnt signaling interacts with other pathways (e.g., STAT3, mTOR). Combining Wnt activation with modulation of these pathways may enhance regenerative outcomes.

Study Limitations

1
The effects of Wnt ligands on axonal growth depend on the cell types with activated Wnt signaling, the type of ligand, the timing of activation relative to the injury, and the site of activation.
2
Off-target effects of Wnt signaling are possible because Wnt/β-catenin induces angiogenesis and tumorigenesis under certain conditions.
3
The signaling and regeneration mechanisms induced by the majority of Wnt ligands remain to be characterized.

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