PUBLICATION
The ubiquitin ligase PHR promotes directional regrowth of spinal zebrafish axons
- Authors
- Bremer, J., Marsden, K.C., Miller, A., Granato, M.
- ID
- ZDB-PUB-190604-1
- Date
- 2019
- Source
- Communications biology 2: 195 (Journal)
- Registered Authors
- Granato, Michael, Marsden, Kurt, Miller, Adam
- Keywords
- Spinal cord diseases, Spinal cord injury
- MeSH Terms
-
- Transgenes
- Cytoplasmic Dyneins/metabolism
- Alleles
- Animals, Genetically Modified
- Spinal Cord Injuries/metabolism
- PubMed
- 31149640 Full text @ Commun Biol
Abstract
To reconnect with their synaptic targets, severed axons need to regrow robustly and directionally along the pre-lesional trajectory. While mechanisms directing axonal regrowth are poorly understood, several proteins direct developmental axon outgrowth, including the ubiquitin ligase PHR (Mycbp2). Invertebrate PHR also limits regrowth of injured axons, whereas its role in vertebrate axonal regrowth remains elusive. Here we took advantage of the high regrowth capacity of spinal zebrafish axons and observed robust and directional regrowth following laser transection of spinal Mauthner axons. We found that PHR directs regrowing axons along the pre-lesional trajectory and across the transection site. At the transection site, initial regrowth of wild-type axons was multidirectional. Over time, misdirected sprouts were corrected in a PHR-dependent manner. Ablation of cyfip2, known to promote F-actin-polymerization and pharmacological inhibition of JNK reduced misdirected regrowth of PHR-deficient axons, suggesting that PHR controls directional Mauthner axonal regrowth through cyfip2- and JNK-dependent pathways.
Genes / Markers
Figure Gallery (8 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping