TY - JOUR T1 - Extrinsic repair of injured dendrites as a paradigm for regeneration by fusion JF - bioRxiv DO - 10.1101/062372 SP - 062372 AU - Meital Oren-Suissa AU - Tamar Gattegno AU - Veronika Kravtsov AU - Benjamin Podbilewicz Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/07/06/062372.abstract N2 - Injury triggers regeneration of axons and dendrites. Research identified factors required for axonal regeneration outside the CNS, but little is known about regeneration triggered by dendrotomy. To determine how neurons regenerate dendrites following injury we study the C. elegans PVD polymodal neurons that display an arborized pattern of repetitive menorah-like structures. We injure dendrites by laser microsurgery, follow their fate and show that broken primary dendrites often regenerate via fusion. We describe how PVD dendrites regenerate and present roles for EFF-1 and AFF-1 glycoproteins in fusion and remodeling of menorahs. Menorahs lose self-avoidance and AFF-1 fuses them, bypassing the injury site. Branch sprouting, EFF-1-mediated pruning, and arbor simplification completes regeneration. When auto-fusion fails the distal arbor degenerates. Surprisingly, AFF-1 acts non-cell autonomously to mediate dendrite fusion. We propose that extracellular vesicles derived from the lateral epidermis fuse severed dendrites in a process reminiscent of enveloped virus-mediated cell fusion without infection.HighlightsNew system to study dendritic plasticity, regeneration and degenerationFollowing dendrotomy AFF-1 is activated to bypass the lesion via auto-fusionExtracellular AFF-1-vesicles derived from the epidermis fuse severed neuronsEFF-1 prunes injury-induced ectopic sproutingCombined activities of the fusogens EFF-1 and AFF-1 regenerate arbors ER -