PUBLICATION

Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish

Authors
Wehner, D., Tsarouchas, T.M., Michael, A., Haase, C., Weidinger, G., Reimer, M.M., Becker, T., Becker, C.G.
ID
ZDB-PUB-170727-6
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.
Abstract
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.
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