PUBLICATION
Robo2 drives target-selective peripheral nerve regeneration in response to glia-derived signals
- Authors
- Murphy, P.L., Isaacman-Beck, J., Granato, M.
- ID
- ZDB-PUB-211221-3
- Date
- 2021
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 42(5): 762-776 (Journal)
- Registered Authors
- Granato, Michael
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Axons/chemistry
- Axons/physiology*
- Motor Neurons/chemistry
- Motor Neurons/physiology
- Nerve Regeneration/physiology*
- Neuroglia/chemistry
- Neuroglia/physiology*
- Peripheral Nerves/chemistry
- Peripheral Nerves/physiology*
- Receptors, Immunologic/analysis
- Receptors, Immunologic/genetics*
- Receptors, Immunologic/metabolism*
- Zebrafish
- Zebrafish Proteins/analysis
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism*
- PubMed
- 34916258 Full text @ J. Neurosci.
Citation
Murphy, P.L., Isaacman-Beck, J., Granato, M. (2021) Robo2 drives target-selective peripheral nerve regeneration in response to glia-derived signals. The Journal of neuroscience : the official journal of the Society for Neuroscience. 42(5):762-776.
Abstract
Peripheral nerves are divided into multiple branches leading to divergent synaptic targets. This poses a remarkable challenge for regenerating axons as they select their original trajectory at nerve branch-points. Despite implications for functional regeneration, the molecular mechanisms underlying target selectivity are not well characterized. Danio Rerio (zebrafish) motor nerves are composed of a ventral and a dorsal branch that diverge at a choice-point, and we have previously shown that regenerating axons faithfully select their original branch and targets. Here we identify Robo2 as a key regulator of target-selective regeneration (sex of experimental subjects unknown). We demonstrate that Robo2 function in regenerating axons is required and sufficient to drive target-selective regeneration, and that Robo2 acts in response to glia located precisely where regenerating axons select the branch-specific trajectory to prevent and correct axonal errors. Combined our results reveal a glia derived mechanism that acts locally via axonal Robo2 to promote target-selective regeneration.SIGNIFICANCE STATEMENT:Despite its relevance for functional recovery, the molecular mechanisms that direct regenerating peripheral nerve axons towards their original targets are not well defined. Zebrafish spinal motor nerves are composed of a dorsal and a ventral branch that diverge at a stereotyped nerve branch-point, providing a unique opportunity to decipher the molecular mechanisms critical for target-selective regeneration. Using a combination of live cell imaging and molecular-genetic manipulations we demonstrate that the robo2 guidance receptor is necessary and sufficient to promote target-selective regeneration. Moreover, we demonstrate that Robo2 is part of a genetic pathway that generates transient, spatially restricted, and tightly coordinated signaling events that direct axons of the dorsal nerve branch towards their original, pre-injury targets.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping