RRC ID 51249
Author Wehner D, Tsarouchas TM, Michael A, Haase C, Weidinger G, Reimer MM, Becker T, Becker CG.
Title Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish.
Journal 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.
Volume 8(1)
Pages 126
Published 2017-7-25
DOI 10.1038/s41467-017-00143-0
PII 10.1038/s41467-017-00143-0
PMID 28743881
PMC PMC5526933
MeSH 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
IF 11.878
Zebrafish Tg(6xTcf/LefBS-miniP:d2EGFP)