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

Armando L. Garcia, Adanna Udeh, Karthik Kalahasty, Abigail S. Hackam

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. 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. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration- promoting genes. 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. Therefore, these studies suggest that Wnt-induced pathways responsible for regulating axonal growth during embryogenesis could be repurposed to promote axonal growth after injury.

Original languageEnglish (US)
Pages (from-to)43-52
Number of pages10
JournalNeural Regeneration Research
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Catenins
Regeneration
Neuroglia
Growth
Growth Cones
Wnt Signaling Pathway
Wounds and Injuries
Spinal Cord Injuries
Embryonic Development
Cicatrix
Axons
Central Nervous System
Ligands
Retinal Neurons
Zebrafish
Neurites
Optic Nerve
Neurosciences
Rodentia
Fishes

Keywords

  • Axonal growth
  • Neuritogenesis
  • Regeneration
  • Retina
  • Retinal ganglion cell
  • Spinal cord
  • Wnt signaling

ASJC Scopus subject areas

  • Developmental Neuroscience

Cite this

A growing field : The regulation of axonal regeneration by Wnt signaling. / Garcia, Armando L.; Udeh, Adanna; Kalahasty, Karthik; Hackam, Abigail S.

In: Neural Regeneration Research, Vol. 13, No. 1, 01.01.2018, p. 43-52.

Research output: Contribution to journalReview article

Garcia, Armando L. ; Udeh, Adanna ; Kalahasty, Karthik ; Hackam, Abigail S. / A growing field : The regulation of axonal regeneration by Wnt signaling. In: Neural Regeneration Research. 2018 ; Vol. 13, No. 1. pp. 43-52.
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