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
-
- Spinal Cord Injuries/genetics
- Spinal Cord Injuries/metabolism
- Spinal Cord Injuries/physiopathology
- Microscopy, Confocal
- Axons/metabolism
- beta Catenin/metabolism
- Larva/genetics
- Larva/metabolism
- Larva/physiology
- Collagen Type XII/genetics
- Collagen Type XII/metabolism*
- Wnt Signaling Pathway*
- Spinal Cord Regeneration*
- Recovery of Function
- Animals, Genetically Modified
- Time-Lapse Imaging/methods
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Animals
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish/physiology
- PubMed
- 28743881 Full text @ Nat. Commun.
Citation
Wehner, D., Tsarouchas, T.M., Michael, A., Haase, C., Weidinger, G., Reimer, M.M., Becker, T., Becker, C.G. (2017) Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish. Nature communications. 8:126.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping