Wnt signaling induces neurite outgrowth in mouse retinal ganglion cells

Adanna Udeh1, Galina Dvoriantchikova1, Tal Carmy1

  • 1Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

Insights

Wingless-type (Wnt) signaling promotes nerve regeneration. Wnt3a directly stimulates retinal ganglion cells (RGCs) to grow more neurites, with Rip kinase signaling influencing neurite number.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Wingless-type (Wnt) signaling pathways are crucial for axonal development in the central nervous system.
  • Canonical Wnt/β-catenin signaling promotes axonal regeneration in adult optic nerves after injury.
  • The precise molecular mechanisms and cellular targets of Wnt-mediated axonal growth remain unclear.

Purpose of the Study:

  • To investigate the cellular mechanisms and target cells of Wnt3a-stimulated neurite growth.
  • To explore the role of candidate mediator genes in Wnt3a-induced axonal growth.
  • To elucidate the involvement of Rip kinases in Wnt-mediated neurite formation.

Main Methods:

  • Primary retinal ganglion cell (RGC) cultures were utilized to study Wnt3a effects.
  • Quantitative PCR (QPCR) was performed to analyze gene expression of candidate mediators.
  • Pharmacological inhibition of Ripk1 signaling using Necrostatin-1s was employed.

Main Results:

  • Wnt3a ligand significantly increased average neurite length and the number of neurites in RGCs in a dose-dependent manner.
  • Wnt3a-dependent neurite growth correlated with decreased expression of Ripk1 and Ripk3 genes.
  • Inhibition of Ripk1 signaling increased neurite number but did not affect neurite length, suggesting Rip signaling modulates neurite number but not length.

Conclusions:

  • Retinal ganglion cells (RGCs) are direct cellular targets of Wnt3a-induced axonal growth.
  • Wnt signaling is associated with Rip kinases in the context of neurite formation.
  • Rip kinase signaling may mediate Wnt3a's effects on neurite number, but not neurite length.

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