Fig. 6: Structural visualization and schematic sequence of EpoB-driven axon regeneration.

a, Cryo-EM image (grid view) of a regenerating axon in the presence of EpoB, 24 h after axotomy. The axotomy site is indicated by a black dotted line. The yellow shading highlights the path of the regenerating axon. Black boxes indicate positions at which cryo-ET data were collected and reconstructed. Sections are shown in b,c. Scale bar, 50 µm. b, Cryo-ET snapshots of a regenerating axon 24 h after axotomy in the presence of EpoB, from the boxed areas in a. Scale bar, 200 nm. c, Segmentation of the cryo-ET reconstructions shown in b. Some areas are surrounded by plasma membranes and some remain uncovered. Growth cones are established at the regenerating axon tip at this time. d, Summary of the molecular events in EpoB-induced axon regeneration. (1) The initial reaction after axon injury or axotomy is membrane closure, resembling the morphology of a retraction bulb. (2) In the presence of EpoB, stabilized microtubules shoot out from the injury site towards the plasma membrane, resulting in increased membrane tension. Using these stabilized microtubules as tracks, tubulin clusters and vesicles as membrane source are shuttled towards the growing axon. (3) Vesicles deliver materials for regeneration, including the necessary membrane support at the regenerating front, resulting in normalizing membrane tension (4). Ultimately, repair is complete, and a new growth cone is established at the axon tip that navigates the growth of the axon.