Repurposing development genes for axonal regeneration following injury: Examining the roles of Wnt signaling

Front. Cell Dev. Biol., 2024 · DOI: 10.3389/fcell.2024.1417928 · Published: May 31, 2024

Regenerative Medicine Neurology Genetics

Simple Explanation

This review explores the connections between developmental embryology and axonal regeneration, focusing on how genes that regulate embryogenesis and CNS development can be used therapeutically to induce regeneration in adult tissues after neuronal injury. The review emphasizes the Wnt signaling pathway and its capacity to initiate axonal regrowth in adult neural tissue within the challenging environment of the injured CNS. The review also examines the potential of other embryonic genes, including Pax, BMP, Ephrin, SOX, CNTF, PTEN, mTOR, and STAT3, to contribute to axonal regeneration in various CNS injury models.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Wnt pathway components may overcome inhibitory conditions following CNS injury and promote axonal regeneration.
2
Upregulation of endogenous non-canonical Wnt5a ligand after optic nerve injury and delivery of recombinant Wnt5a promoted axonal regrowth and retinal ganglion cell (RGC) survival.
3
Other studies showed that Wnt1 and Wnt5a ligands stimulated the non-canonical Wnt-Ryk pathway and inhibited axonal growth in spinal cord injuries.

Research Summary

This review explores the potential of repurposing developmental genes, particularly those involved in embryogenesis and CNS development, for therapeutic induction of axonal and cellular regeneration in adult tissues after neuronal injury. The review emphasizes the Wnt signaling pathway, examining its capacity to initiate axonal regrowth in the challenging environment of the injured CNS, and discusses the roles of other embryonic genes. The review also discusses potential contributions of Müller glia redifferentiation to neuronal regeneration after injury and highlights promising research directions for therapeutic applications of specific embryologic molecular pathways.

Practical Implications

Therapeutic Potential of Developmental Genes

Identifying and manipulating developmental genes like Wnt, BMP, and Pax could lead to new therapies for axonal regeneration after CNS injuries.

Müller Glia Reprogramming for Neuronal Replacement

Understanding the mechanisms of Müller glia reprogramming can help in developing strategies for neuronal replacement and subsequent axonal regeneration.

Targeted Interventions for Axonal Guidance

Developing technologies for precise cell targeting and axonal guidance can improve the efficacy and reduce off-target effects of regenerative therapies.

Study Limitations

1
Limited understanding of how developmental signals are reactivated after injury.
2
Differences between injured and developing CNS tissue affect neuronal responses to pro-regenerative stimuli.
3
Potential off-target effects of therapeutic interventions, such as angiogenesis and tumorigenesis linked to BMPs and Wnt.

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