Abstract
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 language | English |
|---|---|
| Pages (from-to) | E10196-E10205 |
| Number of pages | 10 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 114 |
| Issue number | 47 |
| DOIs | |
| Publication status | Published - 21 Nov 2017 |
Keywords
- Axonal fusion
- Axonal regeneration
- Caenorhabditis elegans
- Nervous system repair
- Phosphatidylserine
Cite this
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Phosphatidylserine save-me signals drive functional recovery of severed axons in Caenorhabditis elegans. / Abay, Zehra C.; Wong, Michelle Yu-Ying; Teoh, Jean-Sébastien; Vijayaraghavan, Tarika; Hilliard, Massimo A.; Neumann, Brent.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 47, 21.11.2017, p. E10196-E10205.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Phosphatidylserine save-me signals drive functional recovery of severed axons in Caenorhabditis elegans
AU - Abay, Zehra C.
AU - Wong, Michelle Yu-Ying
AU - Teoh, Jean-Sébastien
AU - Vijayaraghavan, Tarika
AU - Hilliard, Massimo A.
AU - Neumann, Brent
PY - 2017/11/21
Y1 - 2017/11/21
N2 - 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.
AB - 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.
KW - Axonal fusion
KW - Axonal regeneration
KW - Caenorhabditis elegans
KW - Nervous system repair
KW - Phosphatidylserine
UR - http://www.scopus.com/inward/record.url?scp=85034614638&partnerID=8YFLogxK
U2 - 10.1073/pnas.1703807114
DO - 10.1073/pnas.1703807114
M3 - Article
VL - 114
SP - E10196-E10205
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 47
ER -