ZFIN ID: ZDB-PUB-170727-6
Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish
Wehner, D., Tsarouchas, T.M., Michael, A., Haase, C., Weidinger, G., Reimer, M.M., Becker, T., Becker, C.G.
Date: 2017
Source: Nature communications   8: 126 (Journal)
Registered Authors: Becker, Catherina G., Becker, Thomas, Haase, Christa, Michael, Andria, Reimer, Michell M., Tsarouchas, Themistoklis, Wehner, Daniel, Weidinger, Gilbert
Keywords: Axon and dendritic guidance, Disease model
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Axons/metabolism
  • Collagen Type XII/genetics
  • Collagen Type XII/metabolism*
  • Larva/genetics
  • Larva/metabolism
  • Larva/physiology
  • Microscopy, Confocal
  • Recovery of Function
  • Spinal Cord Injuries/genetics
  • Spinal Cord Injuries/metabolism
  • Spinal Cord Injuries/physiopathology
  • Spinal Cord Regeneration*
  • Time-Lapse Imaging/methods
  • Wnt Signaling Pathway*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • beta Catenin/metabolism
PubMed: 28743881 Full text @ Nat. Commun.
The inhibitory extracellular matrix in a spinal lesion site is a major impediment to axonal regeneration in mammals. In contrast, the extracellular matrix in zebrafish allows substantial axon re-growth, leading to recovery of movement. However, little is known about regulation and composition of the growth-promoting extracellular matrix. Here we demonstrate that activity of the Wnt/β-catenin pathway in fibroblast-like cells in the lesion site is pivotal for axon re-growth and functional recovery. Wnt/β-catenin signaling induces expression of col12a1a/b and deposition of Collagen XII, which is necessary for axons to actively navigate the non-neural lesion site environment. Overexpression of col12a1a rescues the effects of Wnt/β-catenin pathway inhibition and is sufficient to accelerate regeneration. We demonstrate that in a vertebrate of high regenerative capacity, Wnt/β-catenin signaling controls the composition of the lesion site extracellular matrix and we identify Collagen XII as a promoter of axonal regeneration. These findings imply that the Wnt/β-catenin pathway and Collagen XII may be targets for extracellular matrix manipulations in non-regenerating species.Following spinal injury in zebrafish, non-neural cells establish an extracellular matrix to promote axon re-growth but how this is regulated is unclear. Here, the authors show that Wnt/β-catenin signaling in fibroblast-like cells at a lesion activates axon re-growth via deposition of Collagen XII.