Axonal spheroids are regulated by Schwann cells after peripheral nerve injury

Axonal spheroids are hallmark features of neurodegeneration, forming along degenerating axons and contributing to disease progression. Despite their ubiquity across degenerative etiologies, the dynamics of spheroid disappearance, as well as their interactions with glial cells, remain poorly understood. Here, using an in vivo zebrafish model of peripheral nerve injury, we identified several patterns of spheroid disappearance that are regulated by Schwann cells. These results describe spheroid dynamics across their lifetimes, establish a role for the extra-axonal environment in altering spheroid outcomes, and identify a cellular mechanism whereby spheroid fates are altered. Summary Axonal spheroids (also called “dystrophic neurites,” “axonal swellings,” and “axonal beading”) undergo three fates: shrinking, breakdown, and uniform disappearance Schwann cells ensheath most axonal spheroids and internalize a subset of them Schwann cells regulate axonal spheroid fates, identifying a role for axon-extrinsic processes in spheroid regulation Abstract Figure Graphical Abstract: Following injury, spheroids are more likely to undergo shrinking and breakdown when Schwann cells (SCs) are present on degenerating axons. When Schwann cells are absent, spheroids are more likely to undergo uniform disappearance. Spheroids expose phosphatidylserine, which could facilitate interactions between spheroids and SCs.