Phosphatidylserine save-me signals drive functional recovery of severed axons in Caenorhabditis elegans

Zehra C. Abay, Michelle Yu-Ying Wong, Jean-Sébastien Teoh, Tarika Vijayaraghavan, Massimo A. Hilliard, Brent Neumann

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)


Functional regeneration after axonal injury requires transected axons to regrow and reestablish connection with their original target tissue. The spontaneous regenerative mechanism known as axonal fusion provides a highly efficient means of achieving targeted reconnection, as a regrowing axon is able to recognize and fuse with its own detached axon segment, thereby rapidly reestablishing the original axonal tract. Here, we use behavioral assays and fluorescent reporters to show that axonal fusion enables full recovery of function after axotomy of Caenorhabditis elegans mechanosensory neurons. Furthermore, we reveal that the phospholipid phosphatidylserine, which becomes exposed on the damaged axon to function as a “save-me” signal, defines the level of axonal fusion. We also show that successful axonal fusion correlates with the regrowth potential and branching of the proximal fragment and with the retraction length and degeneration of the separated segment. Finally, we identify discrete axonal domains that vary in their propensity to regrow through fusion and show that the level of axonal fusion can be genetically modulated. Taken together, our results reveal that axonal fusion restores full function to injured neurons, is dependent on exposure of phospholipid signals, and is achieved through the balance between regenerative potential and level of degeneration.

Original languageEnglish
Pages (from-to)E10196-E10205
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number47
Publication statusPublished - 21 Nov 2017


  • Axonal fusion
  • Axonal regeneration
  • Caenorhabditis elegans
  • Nervous system repair
  • Phosphatidylserine

Cite this