Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway.

Area of Science:

• Neuroscience
• Cell Biology
• Extracellular Vesicles Research

Background:

• Neuronal polarization is crucial for nervous system development.
• Small extracellular vesicles (sEVs) show potential in promoting neurite outgrowth.
• The role of fibroblast-derived sEVs in central nervous system axon elongation is not well understood.

Purpose of the Study:

• To investigate the effect of fibroblast-derived sEVs on axon outgrowth in mouse primary cortical neurons.
• To elucidate the underlying molecular mechanisms, including the involvement of Wnt signaling and Planar Cell Polarity (PCP) pathway components.
• To compare the effects of sEVs from different cell sources (fibroblasts, neurons, astrocytes) on neuronal axon elongation.

Main Methods:

• Primary culture of mouse embryonic cortical neurons.
• Treatment with fibroblast-derived small extracellular vesicles (sEVs).
• Analysis of axon outgrowth, neuronal morphology, and Wnt-PCP pathway component localization using immunofluorescence and microscopy.

Main Results:

• Fibroblast-derived sEVs significantly promote axon outgrowth and neuronal polarization.
• sEV-induced axon elongation is dependent on endogenous Wnt ligands and core PCP proteins (Prickle, Vangl, Frizzled, Dishevelled).
• Fibroblast sEVs are internalized by neurons, colocalize with Wnt7b, and promote Vangl2 relocalization to the distal axon; sEVs from neurons or astrocytes have different or inhibitory effects.

Conclusions:

• Fibroblast-derived sEVs are potent inducers of axon elongation in central nervous system neurons.
• The pro-axonogenic effect of fibroblast sEVs is mediated by the Wnt-PCP pathway, requiring interaction with endogenous Wnts.
• These findings highlight the specific therapeutic potential of fibroblast-derived sEVs in neural development and repair.