|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.
|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|
|PubMed:||28743881 Full text @ Nat. Commun.|
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.
ABSTRACTThe 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.