PUBLICATION
The synaptic receptor Lrp4 promotes peripheral nerve regeneration
- Authors
- Gribble, K.D., Walker, L.J., Saint-Amant, L., Kuwada, J.Y., Granato, M.
- ID
- ZDB-PUB-180622-30
- Date
- 2018
- Source
- Nature communications 9: 2389 (Journal)
- Registered Authors
- Granato, Michael, Kuwada, John, Saint-Amant, Louis
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Axons/metabolism
- Axons/physiology
- LDL-Receptor Related Proteins/genetics
- LDL-Receptor Related Proteins/metabolism*
- Microscopy, Confocal
- Mutation
- Nerve Regeneration*
- Neuroglia/metabolism
- Neuroglia/physiology
- Peripheral Nerve Injuries/genetics
- Peripheral Nerve Injuries/metabolism*
- Peripheral Nerve Injuries/physiopathology
- Receptor Protein-Tyrosine Kinases/genetics
- Receptor Protein-Tyrosine Kinases/metabolism
- Schwann Cells/metabolism
- Schwann Cells/physiology
- Time-Lapse Imaging
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 29921864 Full text @ Nat. Commun.
Citation
Gribble, K.D., Walker, L.J., Saint-Amant, L., Kuwada, J.Y., Granato, M. (2018) The synaptic receptor Lrp4 promotes peripheral nerve regeneration. Nature communications. 9:2389.
Abstract
Early during PNS regeneration, regenerating axons emerge from the proximal nerve stump, yet whether they extend simultaneously or whether pioneering axons establish a path for follower axons remains unknown. Moreover, the molecular mechanisms underlying robust regeneration are incompletely understood. Using live imaging, we demonstrate that in zebrafish pioneering axons establish a regenerative path for follower axons. We find this process requires the synaptic receptor lrp4, and in lrp4 mutants pioneers are unaffected while follower axons frequently stall at the injury gap, providing evidence for molecular diversity between pioneering and follower axons in regeneration. We demonstrate that Lrp4 promotes regeneration through an axon extrinsic mechanism and independent of membrane anchoring and MuSK co-receptor signaling essential for synaptic development. Finally, we show that Lrp4 coordinates the realignment of denervated Schwann cells with regenerating axons, consistent with a model by which Lrp4 is repurposed to promote sustained peripheral nerve regeneration via axon-glia interactions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping