ZFIN ID: ZDB-PUB-190604-1
The ubiquitin ligase PHR promotes directional regrowth of spinal zebrafish axons
Bremer, J., Marsden, K.C., Miller, A., Granato, M.
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:
  • Actins/metabolism
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Alleles
  • Animals
  • Animals, Genetically Modified
  • Axons/metabolism*
  • Cadherins/metabolism
  • Cytoplasmic Dyneins/metabolism
  • Disease Models, Animal
  • Green Fluorescent Proteins/metabolism
  • Image Processing, Computer-Assisted
  • Ligases/metabolism
  • MAP Kinase Kinase 4/metabolism
  • Mixed Function Oxygenases/metabolism*
  • Mutation
  • Nerve Regeneration*
  • Neuronal Outgrowth*
  • Spinal Cord/pathology
  • Spinal Cord Injuries/metabolism
  • Transgenes
  • Ubiquitin/metabolism
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed: 31149640 Full text @ Commun Biol
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.